As the movie opens, the young Benjamin Franklin Gates (Hunter Gomez) is snooping around an attic when his grandfather, John Adams Gates (Christopher Plummer) catches him. Ben wants to hear the story of the Gates family history, so his grandfather begins reciting:
In 1832, Charles Carroll --- the last surviving signer of the Declaration of Independence --- traveled to the White House, desperate to speak with President Jackson before his death. But, since the President wasn't at the White House that night, Carroll had no choice but to share his closely-guarded secret with his stable boy, Ben's ancestor, Thomas Gates. Carroll told Gates about a fabulous treasure that had existed throughout history, collected by pharaohs and emperors for hundreds of years before being discovered by a group called the Knights Templar. The Knights believed the treasure to be too great for any one man, so they secretly smuggled it out of Europe and over to America. By the time the treasure had been taken to America, the Revolutionary War was raging. The Knights had formed a secondary group called the Freemasons, had recruited members like George Washington, Benjamin Franklin, and Paul Revere, and had formulated a number of secret clues and maps in a desperate attempt to keep the treasure from falling into the hands of the British. As the war ended and time went on, all of the clues were lost except one, the clue belonging to Charles Carroll: "The Secret Lies With Charlotte." Sadly, even Carroll himself didn't know the meaning of that clue.
John's son and Ben's father, Patrick Gates (Jon Voight), comes in to take Ben home. He is obviously skeptical about the existence of the treasure. Ben asks if the Gates family are actually Knights. John does an impromptu ritual, and pronounces Ben to be a Knight Templar to the family Gates.
Many years later, the adult Ben Gates (Nicolas Cage) and his team of researches are traveling across the Arctic Circle. Fellow travelers include the financial backer Ian Howe (Sean Bean) and Ben's friend Riley Poole (Justin Bartha). The group stumbles across a figure buried in the ice. They carve it out using special tools, and find the remains of a ship: the "Charlotte." Ben leads them inside, but the ship's cargo hold only holds barrels with gunpowder... except for one barrel that is guarded by the captain's corpse; the preserved hand holding a musket. Ben opens the barrel and uncovers a carved ivory meerschaum pipe. He discovers a stamp-like imprint on the pipe's base. Coating it with a little of his blood, he rolls the imprint along a paper, and unearths a riddle: "The legend writ, the stain affected. The key in Silence undetected. Fifty-five in iron pen, Mr. Matlack can't offend."
Ben deciphers the riddle step by step: The key and legend both refer to a map, and the stain affected and key in Silence undetected, is a dye or reagent needed to make the next clue visible to the naked eye. Iron refers to a firm resolution, and Timothy Matlack was the scribe for the Continental Congress; 55 members of which signed a resolution that Mr. Matlack penned... the Declaration of Independence. Ian Howe wants to find a way to take a closer look at the document, but Ben is unwilling to take the chance to get close to such a historical artifact. Ian thinks they should steal the Declaration to find the map and the treasure, but Ben flatly refuses. Ian finally turns on Ben and Riley, stealing the pipe and stranding them while setting the Charlotte to blow up. Ben & Riley escape harm and head back to civilization.
Back in the United States, Ben and Riley are meeting with Dr. Abigail Chase (Diane Kruger), an expert in historical documents in charge of the Declaration. Ben uses the alias "Paul Brown" because his family's history doesn't allow for much respect in the academic world. Ben notices that Abigail has a collection of George Washington's campaign buttons but is missing one. Riley and Ben attempt to convince Abigail that someone is attempting to steal the Declaration of Independence because of an invisible treasure map (something they have attempted to convince both the FBI and the DHS and failed). Abigail does not believe them either and sends them out.
Ben decides there is only one option: He and Riley have to steal the Declaration to keep it from falling into the wrong hands. Ben figures out the best way through the security systems would be during an event hosted by the National Archives later that week. Riley manages to patch into the security systems so he can guide Ben through the theft. In the meantime, Ben sends Dr. Chase the missing button for her collection as a gift.
The night of the gala event, Ben manages to infiltrate the gallery disguised in a work uniform with Riley speaking to him over a tiny two-way radio. He quickly switches to a tuxedo and speaks with Dr. Chase, offering her a glass of champagne in order to get her thumbprint, which opens a security door for him. As Ben gets inside, Ian and his group also prepare to infiltrate and take the document.
Ben gets into the Preservation Room with Dr. Chase's password ("Valley Forge") and stands before the Declaration. Just then, Ian's group cuts the security feed, disrupting Riley's video. With no time to lose, Ben takes the entire Declaration case and leaves-only to come face to face with Ian. Ian's henchman shoots at Ben, but it is blocked by the Declaration's bulletproof case. As Ben gets into the elevator, he removes the Declaration from the case and carries it with him. Abigail checks the invitation list and finds that the name Ben used, Paul Brown, isn't on it. Understanding that Abigail is on to him, Ben ducks into a gift shop to escape her notice. He is stopped by a gift shop attendant who thinks he is attempting to steal one of their replica souvenirs. Without enough cash to actually buy one, Ben has no choice but to use his VISA card.
As Ben makes it outside, he is confronted by Abigail --- just as the security alarms go off. Ben tosses the souvenir at her and runs. Abigail is then abducted by Ian, because his team thinks she has the Declaration. Ben and Riley chase after her through downtown Washington, saving Abigail as Ian speeds off.
In Riley's van, Abigail is hysterical until Ben shows her that he has the actual Declaration. Ben also confesses his real name and Abigail recognizes it as "that family with the conspiracy theory about the Founding Fathers."
Back at the National Archives, FBI Agents led by Peter Sadusky (Harvey Keitel) are investigating the theft. Based on the bullets fired, they believe that there were two sets of agents acting in this theft. Sadusky looks up the security files and sees Ben paying with his VISA in the gift shop.
Ben knows they need the Silence Dogood Letters (a pseudonym used in a set of letters written by Benjamin Franklin) for decoding the map (that is the "Key in Silence undetected" mentioned by the riddle.) Since they no longer have the duplicates, they will have to speak with the man who has the originals --- Ben's father.
Patrick is not in any mood to discuss the treasure. He believes that the treasure was merely something invented by Freemasons to keep the British forces occupied during the Revolutionary War.
Ben, Abigail, and Riley finally look at the Declaration of Independence. Abigail carefully swabs some lemon juice along one corner of the back, looking accusingly at Ben when nothing happens. But Patrick reminds them that ferrous sulfate inks only become visible when heat is applied. Ben and Abigail use a blow dryer, and find an Ottendorf cipher referring to lines from Silence Dogood's letters. Patrick explains that he no longer has the letters: they were donated to the Franklin Institute in Philadelphia. When Patrick finds out that Ben has stolen the Declaration, he is speechless. He knows the FBI will be coming to see him soon, so he and Ben come up with an idea to make it look like he wasn't aiding and helping a wanted fugitive.
The FBI storms Patrick's house, finding Patrick tied up and his car missing. Ben and the others are driving to Philadelphia, and Ben decides they should buy some new clothes with the money he took from his father's house.
When they arrive at Philadelphia, Riley (fearful of being spotted) pays a schoolchild to go in and collect the letters for the cipher. Spotting Ian, Riley bolts before he can get the last four letters. Riley catches up to Ben and Abigail (now in new clothes) and shares the new riddle: "The vision to see the treasured past, comes as the timely shadow crosses in front of the house of Pass and..." Riley figures out that the last line is "Stow," referring to Pass & Stow; the casters of the Liberty Bell. Ben thinks the "timely shadow" refers to a specific time they need to be at the Liberty Bell. Looking at a picture of the Bell on the back of a $100 bill, Ben figures that the time is 2:22 pm. Since it is now just 3pm, Ben thinks they have missed it. Riley, surprised that he knows something about history that Ben doesn't know, points out that Daylight Savings Time didn't exist in America until World War One; thus, 3pm today would be 2pm in 1776.
In the meantime, Ian, who'd seen the schoolboy and gotten suspicious, has bribed him to tell Ian what he'd been doing. The schoolboy gives Ian the last four letters, S-T-O-W. Ian googles it, finding the reference to the Liberty Bell.
Ben watches the "timely shadow" fall across the courtyard and finds a brick inscribed with the Freemason's symbol. He carves it out to find an Ocular Device designed by Benjamin Franklin. He puts it on and looks at the map to see the words "Heere at the Wall." Just then, they spot Ian and his group approaching. They split up to try and get away, but Ian ends up getting the Declaration. Ben decides they should meet up again at the car, but he is captured by Federal agents upon his return.
Ben explains the story to Sadusky, who is skeptical. Sadusky asks Ben for his help in recovering the Declaration for them. As Sadusky examines the Ocular Device, Ben realizes that there may be more to the map. Ben gets a call on a cell phone from Ian, who wants the Ocular Device and offers to meet with Ben. The FBI will use this opportunity to arrest Ian and get back the Declaration.
In New York, Ben is on the deck of a battleship with FBI agents undercover all around him. A helicopter flies overhead while one of Ian's henchmen talks to Ben (they used the copter to talk without the FBI observing). Ben walks over to the edge of of the ship's deck and jumps into the Hudson River. As he sinks, a figure in a scuba suit gives Ben an oxygen valve and escorts him to safety.
Ian meets with Ben as he comes out of the water with the Declaration and the Charlotte pipe and explains that the meet-up was a ruse to get Ben out of FBI custody. Ian has made a deal with Riley and Abigail: if he gets Ben out of FBI custody, they will lead Ian directly to the treasure. Ben, with Riley and Abigail observing at an Internet Cafe, takes Ian to a corner of Broadway and Wall Street, telling hims this is where the map leads: "Heere at the Wall;" Heere being the original Dutch name for Broadway.
Ian knows that Ben isn't telling him everything, and he has a contingency plan: He has kidnapped Ben's father and is holding him as a hostage. Ben relents, telling Ian they need to go to Trinity Church (the logo of which was marked by the map's last clue.)
At the Church, Ben and Ian view the Declaration through all three lenses of the Ocular Device, and see the words "Beneath Parkington Lane." They figure out that it refers to an ancient street once located beneath the church. While exploring the church, they find the name "Parkington Lane" engraved on a tombstone of a master Mason. Ian's cronies remove the coffin (destroying the remains in the process) and find a long tunnel. When they reach the bottom, Ben kisses Abigail in an attempt to apologize to her.
They find a huge set of stairs and a dumbwaiter. Upon reaching the bottom, they find an empty room. Riley wonders what to do next and asks Ben to help them. Ben, despondent, snaps and says they are at a dead end. Ian threatens to shoot Ben unless he reveals the next clue. Patrick saves his son by pointing out a lantern hanging in the temple- referring to the lantern in Old North Church in Boston hung during the night of Paul Revere's ride. Ian decides to leave them there and go to Boston; he will only come back if he needs any more help.
As Ian leaves, Abigail quickly points out that there were TWO lanterns in Old North Church, not one, because the British came by sea. Patrick explains that he lied and gave Ian a fake clue to get away. Ben, examining the room, finds an eye symbol on a wall with a slight raised area and deduces that there is indeed another way out of there. They press the raised area, and another door opens into another larger, but still empty, room.
Ben is devastated. He thinks that the treasure is gone and may have even been moved long before the Gates family learned of it. Ben thinks that he has wasted everything. Patrick, on the other hand, is inspired- the very fact that such a room exists proves that the treasure is indeed real.
The Gates' and Abigail vow to keep looking, but Riley points out that they are still trapped. Ben explains that the setup doesn't make sense; builders would've cut a secondary entry shaft to protect against cave-ins during the construction. Ben sees several Freemason symbols engraved on another wall. One of them is a hollow carving resembling the Meerschaum pipe found aboard the Charlotte... 'The Secret lies with Charlotte.' Ben takes the pipe's base apart from its bowl and inserts the bowl into the hollow; using the shaft as a handle. He then rotates the hollow; which opens another door.
The travelers enter a room filled with golden goblets, suits of armor, and other ancient relics. Ben lights a torch in the middle and they see that the room is truly enormous, filled with tens of thousands of artifacts. Patrick rejoices: the treasure has been found! Riley is equally happy; he sees the stairs to get out of there.
Ben meets up with Agent Sadusky and hands over the Declaration of Independence. Ben offers Sadusky a "bribe--" ten billion dollars (his approximation of the treasure's worth). Sadusky recites a quote from the Freemasons about the treasure being too great for any one man; revealing that he is actually one of the Freemasons as well (Ben looks down and sees a Freemason's ring on Sadusky's finger). Sadusky asks Ben what will be done with the treasure. Ben decides that the treasure will be given to the entire world; donated to its most prestigious museums and historical societies (Smithsonian, Louvre, Cairo Museum). Ben gives credit to the entire Gates family and Riley Poole for the find, and insists that Abigail had nothing to do with the theft and should have no bad marks on her record. As for Ben himself, he's desperate to avoid going to prison, but Sadusky repeats, "Somebody's got to go to prison."
In Boston, Ian is breaking into Old North Church when the FBI comes in to arrest him-for kidnapping, attempted murder, and trespassing on government property.
Three months later, Ben and Abigail are dating, and Riley is acting as the group's agent. They've been invited to the grand opening of the treasure exhibits that have been donated to the Cairo Museum. Riley is still upset about their "finder's fee:" Ben was offered 10% of the treasure's worth, but believed that amount was too high and took only 1%, split evenly with Riley. Riley has used part of his money to buy a swanky new Ferrari while Ben has bought a house that once belonged to Charles Carroll.