The film opens in ash-filled woods. A corpse lies rotting on the ground and a malnourished hairless cat climbs over it and begins nibbling at its feet. Nearby a figure in an NBC combat suit lies in wait. An arrow shoots into the cat, killing it instantly. Eli (Denzel Washington) walks over to the cat, plucks out the arrow and bags it for dinner.
Eli walks through the abandoned road in a post-apocalyptic 2043. He is a wanderer and traveling out West. He finds an abandoned house and searches it for anything that can be useful. He tries to fill his canteen with water, but the taps don't work. He checks a closet and finds a dead body. He takes the corpse's boots and clears his weapons while listening to an ancient 3rd Generation iPod. He roasts the cat and eats it, sharing a small portion with a rat that comes close by.
The next morning, Eli wakes up and finds that his iPod is nearly out of power. The car battery rig he uses to charge it is almost out of power as well. Eli continues his journey West and encounters a woman with a broken shopping cart. She asks him for help, but Eli calls out to the thugs hiding nearby, saying he can smell them. The leader pushes Eli around, wanting to rob him; after a single warning, Eli suddenly cuts off the leader's hand with a machete. He fights the other 5 marauders at the same time and kills them all. He kills the leader, robs the corpses of their valuables and walks away, continuing his journey west.
As he continues his journey, his iPod runs out of power. From atop a destroyed highway overpass he witnesses an attack on a couple by a group of marauding bikers. The bikers kill the man, assault the woman and steal all of their books. They drive off, leaving Eli shaken but resolute in his determination not to get involved. He ponders which direction to go in and then ends up walking into a town. He finds the Engineer (Tom Waits) and trades him some KFC wet naps and a Zippo lighter for a recharge on his iPod battery. While he waits, he asks if there is a place where he can fill his canteen. He crosses the street to the bar across the street.
The bikers who killed the couple arrive at the bar and deliver the books and items they stole from the couple to Carnegie (Gary Oldman), the mayor of the makeshift town. Carnegie is looking for a certain book, so he sends his illiterate henchmen to collect all the books they can. He sees the books they bring, a random collection of paperbacks and picture books, and is less than pleased. He orders that they be burned. He takes a hotel bottle of shampoo and tells Redridge (Ray Stevenson), his right hand man, that the bikers are to be rewarded for such a discovery. He goes to his lady, Claudia (Jennifer Beals), and shares the shampoo with her.
Downstairs, Eli trades gloves and an Arab scarf for a full canteen of water. The bartender gives the canteen to Solara (Mila Kunis) and sends her out back to get some water. She goes out back to get the water, but Redridge steps in front of her. She makes him move aside and fills Eli's canteen. In the bar, a cat walks in front of Eli and snarls, he nudges it away. The lead Biker approaches Eli, ready to fight him for touching his cat. Eli slams the thug's face into the bar and gets up to leave. However, the entire bar attacks him. He fights and kills all but one biker, when Solara returns with the canteen and begs Eli to stop. Redridge and Carnegie's men arrive and hold Eli at gunpoint and bring him to Carnegie.
Carnegie is impressed to meet Eli. He recognizes Eli's immense skill and the fact that he is also an educated man who knows scripture. He tells Eli that men like him, who are older but know things, are the future. He asks Eli to stay so that Carnegie can utilize his fighting skills to keep control over the town. Eli tells Carnegie that he has no interest in staying but Carnegie forces him to stay the night.
Redridge sends Claudia to deliver Eli food. He recognizes that Claudia is blind and asks her if she was blind her whole life or blinded by The Flash, an event which occurred during the Last Great War. She confirms that she was blind her whole life. He thanks her for bringing him water. Carnegie decides that the best way to keep Eli in town is to have Solara, Claudia's daughter, sleep with Eli. Claudia begs him not to use Solara, but he sends her anyway. Eli doesn't want to have sex, but Solara begs him to let her stay in the room since she knows Carnegie will harm Claudia. They talk about the war, and Solara sits on the bed, discovers the book and gets excited, wanting to know more about it, even though she can't read. Eli bundles the book up and refuses to discuss it with her. He does share his meal with her, and teaches her to say grace.
The next morning Solara joins Claudia at breakfast. Carnegie freezes in amazement as Solara tries to recite the prayer with her mother. She forgets the 'Amen,' which Carnegie supplies. He then beats Claudia in front of Solara in order to find out if Eli has the book he seeks. When Solara signs him the cross she saw on the cover, Carnegie orders Redridge to bring the book to him. When they get to the room, they see that Eli had snuck out. Redridge kills the guard on duty and gathers the men to find him. Across the street, Eli gathers his battery and prepares to leave.
Carnegie goes over to Eli and begs him to stay and give him the book, a Bible. Carnegie tells Eli that he isn't afraid to kill him and take the Bible. Carnegie thinks that the Bible's righteous scripture is the best way to keep the town under his control. Eli tells Carnegie that he dreams of finding a town where the people need the book, but he tells Carnegie that it is not here. Carnegie orders Redridge to shoot Eli as he walks away but Redridge misses twice. A shootout ensues and Eli kills most of Carnegie's men and hits Carnegie in the knee. Redridge sees that Eli is fearless and begrudgingly lets him leave. Behind the scenes, Claudia tells Solara to follow Eli, since she will be safer away from Carnegie.
Carnegie gets his leg treated by a doctor. The bullet and shrapnel are removed and he is bandaged. He tells Redridge to prepare the vehicles to pursue Eli and recover the book. Redridge tells Carnegie that most of their men are dead and decides to use the book as leverage to get Solara as his concubine. Carnegie humorously, albeit reluctantly, agrees.
Eli travels down the road until Solara catches up to him. She wants to join him but she is rejected from the start. She offers to take him to the town's water supply, an uncontaminated underground spring. Eli fills his canteen at the spring, then tricks Solara and locks her in the cave. She screams and calls him a liar but Eli insists that he isn't, wishing her well and leaves.
Somehow Solara breaks out of the cave and follows in the direction Eli was going. She doesn't find him, but instead finds the woman who worked with the thugs from earlier with her broken cart. She tries to help the woman, but the woman insists that Solara leave to keep from being raped and killed. Two thugs attack Solara and just as they are about to rape her, Eli shoots one through the groin with an arrow and then shoots the other through the throat. Solara desperately hugs Eli and the two go on their way.
Carnegie and Redridge's men find the bodies of the marauders and determine that Eli can't be more than a few miles ahead. Redridge finds a piece of Solara's custom clothing and tells Carnegie with displeasure. Carnegie asks if Redridge still wants her and walks back to the car. One of their henchmen suggests that they call it a day, since their cars will give them away at night and they could drive right by the pair.
Eli and Solara sleep by an old nuclear plant cooling tower. Eli reads the book and Solara asks Eli to read it to him. He recites a bit of it and then puts the book away. She asks him to teach her how to read it but Eli doesn't respond. When she thinks he's asleep she goes to take a look at the book in his bag. She sees (but can't read) an old KMart tag which says "Hi, my name is Eli". Eli grabs the bag away from her and makes her go back across the room, cocking his shotgun to make her know how serious he is.
The next day the pair set off and walk west. Solara asks him about the world before the war. He tells her that people had more than they needed and threw away things that others kill for today. She asks him why he keeps the book and Eli explains that it is the only Bible left in the world since it was singled out for extermination after the war, as the post-war population believed it was the cause of the war. He then explains why he keeps heading west, which perplexes Solara but she eventually comes to accept that Eli is acting on his faith. He explains how he found the Bible, insisting that a "voice" told him where to go and that he would be protected. Solara thinks that Eli is delusional but says nothing.
The pair arrives at an old house with a sign that says "No Trespassing." Eli tries to open the door, but a trap opens up and the two fall into a hole. They find themselves at the mercy of Martha (Frances de la Tour) and George (Michael Gambon), an elderly couple who have lived in their house for years. They ask why they didn't obey the sign and Eli apologizes, saying he didn't see it. They give Eli and Solara tea and then show them a cemetery filled with the people who attacked their house. Eli tells Solara that it's time to go, explaining that Martha had 'the shakes' because the couple are cannibals who ate their victims and could have drugged the tea. As they leave, Carnegie's caravan passes and sees the pair exiting the house. Eli and Solara re-enter the house and George and Martha pull out an impressive gun cache from under the sofa.
A stand off ensues. Carnegie tells Eli to throw out the book. Everyone is ready for the gunfight. A covered parcel is hurled through the window. Redridge looks at it and realizes it's a bomb, throwing it away and running for cover. Two cars explode, killing several men. Eli and the house's occupants fire their weapons until Redridge pulls out an RPG missile and blows half the house up, killing Martha. George starts shooting wildly, killing men left and right until Carnegie's men bring out a hand operated Gatling gun and blast him away along with most of the house. Eli and Solara are surrounded and dragged out of the house.
Carnegie threatens to kill Solara, to the dismay of Redridge. Redridge entreats Eli to surrender the book and Eli tells Redridge where he hid it. Redridge recovers the book, with a locked flap, and gives it to Carnegie, who releases Solara. He says God is good. and Eli responds "all the time." Carnegie responds "Well. Not all the time" and shoots Eli in the stomach. He puts Solara in one van with Redridge and a driver and then takes the book with him in the other.
In the other van, Redridge puts Eli's machete on the dashboard and chuckles to himself now that Eli is gone. Solara uses the wire from Eli's bow that she had in her pocket and chokes the driver until the car flips over. The driver is killed and Carnegie's men turn around to go to the accident site. Solara throws a grenade, blowing up the third car. Solara goes to the driver's seat and sees Redridge was impaled by Eli's machete. He pulls the machete out and steps out of the vehicle with grace. Collapsing on his knees in penance, he dies. Solara drives away and Carnegie opts not to go after her since he has the book and they have barely enough fuel to get back to town.
Solara returns to the house and finds that Eli is missing. She finds him still walking west. She puts him in the car and he treats the gun shot wound with duct tape. She apologizes for losing Eli's book but Eli responds that it's time he put the lessons he learned to use: to do more for others than you do for yourself. They drive to the remnants of the Golden Gate Bridge and Eli says that they are close. He finds a row boat and starts to row toward Alcatraz Island. Fatigue and weakness overtake him, so Solara takes over. An armed guard calls out to the pair and Eli responds that he has in his possession a King James Bible. The guard lets him in.
Eli is taken to Lombardi (Malcolm McDowell), the curator of Alcatraz, who has been gathering all the remnants of pre-war civilization, such as books, music, and art, and storing them in the cells until they are ready to rebuild and re-establish society. Lombardi tells Eli that they have been missing a copy of the Bible, so Eli tells him to get a lot of paper and pen. He starts to recite the Bible word for word, having memorized it over the last 30 years.
Back in town, Carnegie tries to open the bible but realizes that he didn't take Eli's key to the book flap. He calls the Engineer in to unlock the book and once it's unlocked they see the Bible is in Braille. Carnegie tries to get Claudia to read it but she cruelly lies and tells him that she's forgotten how. She tells him that his leg smells and that he's feverish: signs of an infection. The rest of the town's populace is looting the bar and Carnegie's remaining men are fighting each other; in his quest for the book, Carnegie has lost control and the town has erupted into anarchy. He collapses in despair.
In Alcatraz, Eli shaves all his hair and changes into a clean white robe. He recites the Bible to completion while Lombardi writes it down verbatim. Eli eventually dies from his gunshot wound but completes his task. In a voiceover he utters one last prayer for Solara and the world before he dies. He is buried in Alcatraz's courtyard garden. Lombardi places a newly typeset and bound copy of the Bible on a bookshelf in a massive library, where a place has been saved specifically for it. Solara pays her respects, takes Eli's machete and iPod and leaves Alcatraz, walking down the open road.