As a young boy in Indiana, Abraham Lincoln witnesses the death of his mother, Nancy, which he soon discovers was caused by the bite of a vampire. Vowing revenge, Lincoln dedicates his life to eradicating the creatures responsible. His quest for vengeance is complicated by his realization that vampires are not only powerful but entrenched within American society. Lincoln's hatred of vampires becomes rooted in a deeper understanding that they are intertwined with the institution of slavery, feeding off the blood of slaves.

Years pass, and Lincoln befriends Henry Sturges, a mysterious figure who trains him in vampire hunting. Armed with his silver-tipped axe, Lincoln sets out to execute vampires and their human collaborators. His path crosses with Mary Todd, whom he eventually marries. Lincoln's fight against the supernatural beings is set against the backdrop of his rising political career. As he ascends to the presidency, his dual life unfolds on a grand scale, with the country's very fate hanging in the balance as he confronts a nation where vampires thrive on the chaos of the impending Civil War.