Abraham Lincoln (Benjamin Walker) witnesses the death of his mother by the vampire Jack Barts, and vows revenge. He becomes a vampire hunter, trained by the vampire Henry Sturges (Dominic Cooper), who didn't want to be turned, and kills Barts. After this, he woos and marries Mary Todd Lincoln (Mary Elizabeth Winstead), and turns to politics to defeat the evils of slavery.
The forces of the Confederacy, however, ally themselves with the vampires (Vampires use slaves for food), and vampire leaders Adam and Vadoma (Rufus Sewell and Erin Wasson) send vampires to assist the troops in Gettysburg. Vadoma also kills Lincoln's son Willie. To stop the vampires and save the Union, Abraham, Henry, and his friends Joshua Speed and Will Johnson gather up all the silver in Washington DC (Silver kills vampires) and set off on a train to Gettysburg. Adam stops the train by setting fire to a bridge, and (anachronistically) kills Speed, but is killed by Abraham, who punches through his chest with the silver pocketwatch he got from Henry.
It turns out the silver was actually taken to Gettysburg in secret by Mary Todd and Harriet Tubman, and arrives in time to be made into bullets. The Union is saved, and Mary Todd kills Vadoma for good measure.
The movie ends with Abraham heading off to Ford's Theatre (where he will be assassinated), and with Henry meeting with another potential vampire hunter in modern times.
Thanks Paul B!