In 1818, Abraham Lincoln (Benjamin Walker
) lives in Indiana with his parents, Nancy (Robin McLeavy
) and Thomas (Joseph Mawle
), who works at a plantation owned by Jack Barts (Marton Csokas
). There, Lincoln befriends a young African American boy, William Johnson (Anthony Mackie
), and intervenes when he sees Johnson being beaten by a slaver. Because of his son's actions, Thomas is fired. That night, Lincoln sees Barts break into his house and attack Nancy. She falls ill the following day, and dies shortly afterwards. Thomas tells Lincoln that Barts poisoned Nancy.
Nine years later, Lincoln decides to get revenge against Barts. He attacks Barts at the docks, but Barts, who is actually a vampire, overpowers him. However, before Barts can kill him, Lincoln is rescued by Henry Sturgess (Dominic Cooper
). Sturgess explains that vampires exist, and offers to teach Lincoln to be a vampire hunter. Lincoln accepts and, after a decade of training, travels to Springfield, Illinois. During his training, Sturgess tells Lincoln that the vampires in America descend from Adam (Rufus Sewell
), a vampire who owns a plantation in New Orleans with his sister, Vadoma (Erin Wasson
). Sturgess also tells Lincoln of the vampires' weakness, silver, and presents him with a silver pocket watch.
In Springfield, Lincoln befriends shopkeeper Joshua Speed (Jimmi Simpson
), and meets Mary Todd (Mary Elizabeth Winstead
). Though Sturgess warned him not to form any close relationships, Lincoln develops romantic feelings for Mary.
Lincoln successfully finds and defeats Barts. Before dying, Barts reveals that Sturgess is also a vampire. Lincoln confronts Sturgess, who reveals that, several years ago, he was attacked and bitten by Adam. Because Sturgess' soul was impure, he became a vampire, and that prevented him from harming Adam or any other vampire (since "Only the living can kill the dead"). Sturgess has since been training vampire hunters, hoping to destroy Adam.
Disappointed, Lincoln decides to abandon his mission. However, Adam learns of his activities and kidnaps Johnson to lure Lincoln into a trap at his plantation. Adam captures Lincoln and tries to recruit him, revealing his plans to turn the United States into a nation of the undead. Speed rescues his friends, and they escape to Ohio.
Lincoln marries Mary and begins his political career, campaigning to abolish slavery. Sturgess warns Lincoln that the slave trade keeps vampires under control, as vampires use slaves for food, and if Lincoln interferes, the vampires will retaliate. After Lincoln's election as President of the United States of America, he moves to the White House with Mary, where they have a son, William Wallace Lincoln (Cameron M. Brown
). He eventually signs the Emancipation Proclamation, setting the American Civil War in motion. William is later bitten by Vadoma and dies.
Confederate President Jefferson Davis (John Rothman
) convinces Adam to deploy his vampires on the front lines. Lincoln orders the confiscation of all the silverware in the area and has it melted to produce silver weapons. Speed, believing that Lincoln will lead them to death, defects and informs Adam that Lincoln will transport the silver by train.
On the train, Adam and Vadoma attack Lincoln, Sturgess, and Johnson, who have set fire to the upcoming trestle. During the fight, in which Speed is killed, Adam learns that the train holds only rocks. Lincoln reveals that Speed's betrayal was a ruse to lure Adam into a trap. Lincoln uses his watch to stab Adam, killing him, and the three escape the train before it explodes. Meanwhile, Mary and the ex-slaves have transported the silver to Gettysburg through the Underground Railroad.
The now leaderless Confederate vampires stage a final, massive assault and are met head on by the Union. Armed with their silver weapons, the Union soldiers destroy the vampires and win the war.
A few months later, on April 14, 1865, Sturgess tells Lincoln that the remaining vampires have fled the country. Sturgess unsuccessfully tries to convince Lincoln to allow him to turn Lincoln into a vampire, so that he can become immortal and continue to fight vampires. That night, John Wilkes Booth kills Lincoln.
In modern times, Sturgess approaches a young man at a bar in Washington, D.C. as he once approached Lincoln.