Thirty years after an apocalyptic event, Eli (Denzel Washington) is on a journey to the west coast of the United States. On his travels he runs into many enemies, but he ably dispatches them with his fighting skills.

Searching for a source of water he arrives in a ramshackle town which is overseen by Carnegie (Gary Oldman). Carnegie is a literate man and he has gangs looking for a book, though the gangs and his own henchmen do not understand why he wants the book.

After shooing away a cat in Carnegie's bar, Eli is set upon by a gang of bikers; Eli kills them all. Realizing that Eli is a literate man like himself Carnegie asks Eli to stay, though it is made clear that the offer is not negotiable. After Carnegie's blind wife Claudia (Jennifer Beals) gives Eli some food Carnegie asks Claudia's daughter Solara (Mila Kunis) to seduce Eli. Eli turns her down but before they eat he says a prayer.

The following day Solara prays with her mother and Carnegie realizes that Eli has a copy of the Bible, the book he has been looking for, as all copies were destroyed after the apocalypse. Eli sneaks out of his room and goes to the stores across the street where he asked the Engineer (Tom Waits) to recharge his portable battery.

Carnegie attempts to stop Eli, having all his henchmen fire at him, but Eli appears to be invulnerable to bullets and he shoots most of Carnegie's henchmen, and a ricochet shot grazes Carnegie's leg. After Eli leaves, Solara follows and tracks him down; she takes him to the town's water supply and Eli traps her there and continues on.

Solara escapes and finds herself set upon by two men, whom Eli kills and they continue on until they arrive at a house. The residents Martha (Frances de la Tour) and George (Michael Gambon) have fortified their house and Solara and Eli fall through a trap door, but George and Martha invite them in for tea. Eli surmises that they trap and kill guests but before Eli and Solara can leave they are found by Carnegie.

After a shoot-out which kills some of Carnegie's men, George and Martha are killed, and Eli and Solara are captured. Carnegie threatens to kill Solara and Eli hands the Bible over to Carnegie. Carnegie shoots him in the stomach and leaves. While in transit Solara escapes and drives back to help Eli, Carnegie returns to the town as he has the Bible and is low on fuel.

Solara picks Eli up and they continue west until they reach the Golden Gate Bridge, then they row over to Alcatraz where they find a group of survivors dedicated to preserving pre-war knowledge. Eli tells the guard that he has a copy of the King James version of the Bible and they are allowed in. Inside they are introduced to Lombardi (Malcolm McDowell), who is the curator of a collection of things from before the apocalypse. Eli, who is possibly blind (a heavily debated plot point), dictates the Bible from memory to Lombardi, then dies from his wounds. Carnegie has the Engineer open the Bible but is distraught to find that it is in Braille, and his wife refuses to read it to him. His leg has started to go septic and he will die without ever having read the Bible.

Alcatraz prints copies of the Bible, Solara takes Eli's weapons and heads back east to the town.