In a boat off the coast of Panama, reporter Elena Fisher records footage of Nathan Drake as he retrieves the coffin of legendary explorer Sir Francis Drake, believed to have been buried at sea some 400 years previously.
Nate, who claims to be a direct bloodline descendant of Sir Francis (a point Elena disputes - history documents him as dying without a heir), opens the lead casket to find not dry bones amidst the ballast, but a sealed strongbox. Elena is surprised, but Nate clearly anticipated this. Opening the box, he triumphantly retrieves a small, leather-bound journal. Inside, every page is covered with hand-drawn charts, illustrations and notes in a fine 16th-century script.
Though Elena's company paid for the expedition, Nate has no desire to share this prize ("The deal was for a coffin"), much to the reporter's annoyance. Before the argument can develop, Nate is alarmed to spot incoming boats, and the pair are forced to fight off an attack by pirates. Though the onslaught is repelled, their boat is destroyed. They are rescued from the ocean by Victor Sullivan: Nate's cigar-chomping friend and business partner.
At a dock on a tropical shore, Elena talks to her irate producer on a cellphone as Nate and Sully discuss Drake's journal. It confirms, to Nate, a longstanding belief that the explorer faked his death.
"When Drake sailed into the Pacific," Nate explains, "he took the Spanish fleet completely by surprise. He captured their ships, he took all their maps, their letters, their journals - and he recorded everything in this diary. But when he got back to England, Queen Elizabeth confiscated all of his charts and logbooks - including this one - and swore his entire crew to silence. Y'see, Drake discovered something on that voyage, Sully - something so secret, and so valuable, they couldn't risk it getting out..."
With unconcealed glee, Nate presents to Sully the final page of the journal: a meticulously detailed map of an area in the Amazon, complete with coordinates, and one location highlighted: El Dorado! The lost city of gold...
With a prize this large at stake, Sully persuades a reluctant Nate that they should abandon the reporter - and their boat roars away as the furious Elena pounds along the dock in pursuit.
A week later, deep in the Amazon, Nate and Sully enter an ancient pre-Incan temple at the coordinates marked in Drake's journal. They find walls lined not with gold, but embedded skulls. This is a place where death was worshipped.
Tracing reliefs once inlaid with precious metals and fine jewels, now scarred by scrapes and pitted holes that bear witness to long-past plunder, Nate observes that the temple was picked clean centuries before. A 16th-century conquistador's helmet found in the rubble suggests that the Spanish arrived before Drake. Sully is furious: he's deeply in debt, and has no use for such common-or-garden antiquities.
Deeper inside the temple, the duo reach a final chamber with an empty dais: a platform where something of great significance once stood. They learn, studying a ruined wall relief, that El Dorado was not a city, nor even a temple, but a huge golden idol of incalculable value. The Spanish, they reason, must have dragged it from the temple on cut logs. Nate and Sully set out to follow the centuries-old tracks.
On leaving the temple, Nate and Sully behold an incredible sight: a World-War-II-era German submarine perched in a shallow pool above a waterfall.
Sully is spooked: "Something about this feels kinda hinky," he mutters.
Nate, less so: "Hinky? You act like you've never seen a German U-boat in the middle of the jungle before."
Nate volunteers to go on board alone. Realising that he must swim to reach the entrance, he hands Drake's journal to his partner. Inside, he finds a mummified crewman with pockets full of 16th-century Spanish coins. Further into the vessel he arrives in private quarters where a skeleton in a captain's uniform lies with a Luger pistol beside it. Judging by the tears in the decayed cloth, the bunk sheets behind splattered and stained with blood, Nate remarks that the captain appears to have been torn to shreds.
Searching the corpse, Nate finds a map on a piece of paper with a tear matching a missing page in Drake's journal. On a nearby desk lies another map. Nate realises that the shorelines match: both document the location of an uncharted island in the South Pacific. Making a note of the coordinates, and alarmed by Sully's sudden radio silence, he returns outside.
Nate finds Sully held at gunpoint by armed mercenaries in the employ of Gabriel Roman and his lieutenant, Atoq Navarro. Sully, it transpires, owes Roman a substantial sum of money, and used the promise of "the find of a lifetime" as collateral to buy more time.
Roman takes the German map from Nate (though is unaware of the other copy), and seems poised to execute him; when Sully intervenes, he is shot in the chest and crumples to the ground. As an apoplectic Nate is restrained by Navarro, a torpedo he disturbed on his journey through the U-boat detonates, knocking all present from their feet.
In the momentary confusion Nate escapes, bullet whistling around him as the mercenaries pursue him.
Returning to the temple entrance, two arms reach out to grab Nate's shirt and haul him behind a pillar. He turns to swing at his attacker - only to recognise his assailant as Elena. He drops his guard...and is rewarded by a sharp punch to the face.
Though furious about the earlier abandonment, Elena softens as Nate explains that Sully is dead. Together, they escape the mercenaries. Nate speculates that the Spanish moved El Dorado to the island marked by the coordinates found on the U-boat, and were followed there by Sir Francis Drake. Though aware that Gabriel Roman and his personal army may lie in wait, they resolve to continue their pursuit of the ancient treasure.
As Nate and Elena fly above the South Pacific island, their seaplane is buffed by anti-aircraft fire. Forced to parachute to safety, the pair are separated. After a rough landing due to a faulty parachute, Nate regains consciousness in the branches of a tree. He fights through a ragtag but heavily armed cohort of pirates evidently sent to search for survivors, and retrieves Drake's map from the plane's cockpit. Spotting Elena's parachute flapping in the distance on a cliff-top fort, he sets off to find her.
After further skirmishes with pirates and a perilous climb on the exterior wall of the fortress, Nate is knocked out by an explosion. He is later awakened in a jail by Elena outside the small cell window. She observes the composition of the wall, and remarks that it would require little effort to tear it down. She disappears as Eddy Raja, leader of the pirate forces on the island, arrives to question Nate.
Raja and Nate are old acquaintances - but far from friends. The pirate captain has Drake's map and suggests that Nate lead him to the treasure.
Nate chuckles humourlessly: "Is that it? Is that my deal? Die now, or help you and die later. It's a tough call, but you know what? I'll take 'die now. "
Raja is furious: "Tai kamu! Listen to me, maggot - I was promised treasure on this goddamn rock! And now my men are dying. They can't go outside to take a piss without an armed guard, and I have nothing to show for it!"
As Raja talks, the back wall of the jail suddenly collapses - revealing Elena outside behind the wheel of a 4x4 with a front-mounted winch. Exploiting the distraction, Nate snatches Drake's map from Raja's hands and leaps into the waiting vehicle.
After a breakneck vehicular pursuit through jungle paths and clifftop tracks, the protagonists find themselves hanging precariously over a broken bridge. Eddy Raja arrives and demands that Nate hand over the map. Upon warning Elena to hold tight, Nate sends the vehicle into reverse - pitching it into the water far below.
Nate and Elena survive the fall, then fight pirates send to kill them. Later, as Elena reviews footage on her camera, she draws Nate's attention to the harbour area and suggests that the Spanish must have brought all cargo in that way - including El Dorado. Nate, however, concentrates on another point of interest, noticing a modern-day boat among the wrecked galleons.
Nate insists that escape is their only priority - "I don't need your bullet-riddled corpse on my conscience" - but Elena disputes his concern, then wryly suggests that because they must travel to the harbour anyway, they should argue about it on arrival. Finding an unattended jetski, they travel along waterways to reach the settlement.
Inside the hall of records, Nate scours the shipping manifests. He finds the volume he is seeking lad out, and reads the Spanish script with apparent ease.
Elena is impressed: "Look at you, Mr. Translator. Not just a grave robber after all, huh?"
Nate finds a reference to a gold statue, with a weight that could correspond to that of the El Dorado idol. They regard an illustration of it within the ledger and are both taken aback. It is quite distinctly grotesque. Nate turns the page...and finds the remaining sheets ominously blank.
As he thoughtfully plays with a ring on a cord around his neck, Elena enquires about its significance. Nate reveals the identity of its original owner, and they examine inscriptions on its surface. It features Sir Francis Drake's motto ("Sic parvis magna - "greatness from small beginnings), a date (one day after Drake's supposed death), and a set of coordinates: the exact position of the coffin off the coast of Panama...
The pair separate as Nate sets off to steal the pirate boat.
Nate approaches the boat and appraises the scene, poised to attack the pirates on board. Suddenly, Elena arrives beside him and insists that he watch footage on her camera. It's Sully: alive, unharmed, and in the company of the antagonists. Elena delicately enquires how much Nate trusts his old friend.
Nate holsters his pistol, and appears resolute: "Sully's a lot of things, but he's not a backstabber."
Vowing to either rescue his friend, or "beat the crap out of him" in the event of a double-cross, Nate and Elena set off in pursuit.
During the journey to the mountain monastery to find Sully, Nate and Elena encounter crude but vicious traps hidden in the undergrowth. Once has been sprung; as they regard the ensnared corpse of a pirate, they comment that he appears to have been eaten or savaged by some form of creature. Bizarrely, the mechanism has been constructed using materials from Nate's crashed plane.
Elena remarks that this makes no sense. Why would the bad guys set deadly traps such as these when the island is crawling with their own men? The duo suspect they are being watched, and comment that the usually noisy jungle is strangely quiet.
Infiltrating the monastery, Nate and Elena discover that Sully is being held hostage; they free him from his captors. Sully reveals that Drake's journal, held in his breast pocket, stopped the bullet for him - a miraculous escape, though the impact still knocked him senseless. Having convinced Roman that he could have helped find El Dorado, he has supplied a stream of misinformation to buy time.
Putting together clues on the location of the treasure vault, the trio find a hidden library, where Nate enters an underground network of catacombs.
Inside the tunnels, Nate spies on a meeting between Eddy Raja and Gabriel Roman. Raja is deeply disturbed by the massacre of his men. Roman is disparaging: he believes these casualties have been caused by Nate alone, and scoffs that they should have all fallen to one man. Raja, however, truly believes the island to be "cursed".
Roman announces that he has no further need for the services of Raja and his mob. With Navarro's gun leveled at his chest, the pirate leader flicks his cigarette contemptously and departs in a rage. Roman discusses the situation with his right-hand man. They agree that Sullivan cannot be trusted - "He knows we'll kill him once we find the treasure. He has no incentive to tell the truth" - but it becomes clear that Navarro finds his employer's imperious manner difficult. The purusit of El Dorado, we learn, is his passion; the wealthy Roman is growing weary of it. "Chasing this treasure of yours," he condescends, "is proving to be more trouble than it's probably worth."
Nate, Sully and Elena reach an elaborate octagonal mausoleum where, following prompts in Drake's diary, Nate uncovers the secret entrance to the Spanish treasure vault. Separated from Sully by a trap mechanism, Nate and Elena venture into the depths to negotiate an arcane underground maze.
At the heart of the vast, sprawling labyrinth, El Dorado is nowhere to be seen. They find the chamber long since picked clean, except for one poignant detail: the body of Sir Francis Drake. Nate, clearly saddened that the explorer died here having failed to claim the idol, returns his ring to its rightful owner. The moment is shattered by shouts, screams and gunfire.
Eddy Raja and a single pirate burst into the room, clearly terrified. Moments later, the source of their fear becomes apparent as humanoid monstrosities with dead, black eyes, cruel teeth and long claws emerge from the shadows. Raja's pirate companion is dragged screaming into the pit below...and the onslaught begins.
Nate and the pirate leader fight back-to-back during the ensuing assault, their enmity set aside in a desperate battle to survive. Raja falls to a swarm of the creatures, despite Nate's heroic attempts to rescue him, and all seems lost - until Elena provides a last-minute avenue of escape.
Fleeing the pursuing mutants, Nate and Elena are astonished to arrive in the control room of an abandoned WWII-era military facility. They find a schematic revealing that the Germans removed El Dorado from the Spanish treasure vault and transported it to another location beneath the monastery. With the facility locked down, Nate leaves Elena behind to reach the generator room.
After restoring power Nate begins the return journey, but passes through a room where a movie projector is now running. It tells a brief but chilling tale, documenting a young German soldier chained in place, his eyes black, his mouth covered with what appears to be blood, attempting to lunge at the cameraman. The El Dorado statue is a looming presence in the background.
On the table beside the projector, Nate notices a weathered sheet of paper and a picture showing Sir Francis Drake's body at the foot of the El Dorado statue in the Spanish vault. The document is his valediction:
"My end is near. The devils hunt for me in the darkness. The gold of El Dorado bears a terrible curse; the Spaniards have unleashed hell, and become as demons. My men have all been murdered, leaving the task to me. No ship will depart this island; I destroyed them all, and drowned the cursed city. A thing of such great evil must never leave these shores. In my final hour, I comment my sould to God. May He have mercy on this unholy place."
Understanding the significance of Drake's final words and his noble sacrifice, Nate rushes to find his friends.
Back at the control room, Nater returns to find Elena being taken hostage by Roman, who mockingly waves the schematics revealing the location of El Dorado. Nate battles against the monstrous, indigenous creatures and Navarro's most elite mercenaries until, reunited with Sully, the duo enter the subterranean grotto, where they lay eyes on the El Dorado idol. When their ambush is foiled before it can begin, they watch on at gunpoint as Roman regards the statue, ten feet high, solid gold and adorned with fine jewels.
Navarro informs his employer that the true treasure of El Dorado lies inside the idol. Finding a hidden catch, Roman opens it to reveal a hideously deformed mummified corpse. There are audible gasps from all present at the revelation that El Dorado is not a statue, but a sarcophagus - with the exception of the grinning Navarro.
Ancient motes of dust drift from the corpse. As Roman inhales these he chokes, slamming the sarcophagus shut. His last rational act is to roar his betrayer's name as an appalling transformation takes place. Black-eyed and feral he rushes at his lieutenant...who regards his approach with detached interest, then calmly dispatches him with a single shot to the head.
As El Dorado is secured within a cargo net and tethered to a helicopter hovering above, Navarro contemptously berates the main charactes for their lack of imagination. The real profit, he exults, lies neither in the value of the gold nor the jewels, but the virulent mutagen held within.
Sibilant whispering fills the air. Nate reveals the origin of the creatures as they begin their attack: "The Spanish, Sully - they never left!"
In the ensuing chaso, Nate and Sully make their escape. Nate jumps onto the cargo net holding El Dorado, and hangs precariously beneath the helicopter. When a mercenary attempts to shoot him, Elena - still held hostage in the cabin above - lashes out and kicks him through the doorway. His rifle discharges as he falls, killing the pilot, and the helicopter careends towards the deck of Roman's ship in the harbour...
As Elena lies in the wreckage, balanced precariously on the side of the ship, Nate fights a desperate battle against Navarro and his remaining mercenaries. When the two finally clash directly on the upper deck, Nate beats Navarro unconscious and runs to the reporter's aid. Pulling her to safety, he finds her alive and regaining consciousness... but turns to see Navarro holding a gun on them. Nate glances at his adversary's feet, and notices a coiled loop of cable tethering the sarcophagus to the helicopter. Quick as a flash, he pushes the wreckage with all his might. Navarro is ensnared by the cord, and dragged screaming into the depths.
In the aftermath, Elena presents Nate with a significant gift: Drake's ring, retrieved without his knowledge earlier. Sully arrives in a boat and joyfully reveals an assortment of treasures taken from pirates "too dead to care".
Later, Nate apologises that Elena didn't get her story; she retorts that there will be others, and that Nate still owes her one.
"I'm good for it," he smiles, as their boat moves from the harbour into the open sea.