A small-town English teacher, Jake Epping, learns from a friend that there is a portal that leads from the present back to 1960. Jake's friend asks him to help him stop John F. Kennedy's assassination by going back in time and finding out who really killed Kennedy... and killing them.

Unnerved by the impossibility of his mission, Jake travels to Holden, Kentucky in order to save the family of his friend Harry Dunning, who were all murdered on Halloween by Harry’s father Frank. But does Jake have what it takes to kill a man?

Jake finds an unlikely ally in his quest in local drifter Bill Turcote. He gets a teaching job in a small town near Dallas and discovers romantic sparks with school librarian Sadie Dunhill. Jake constructs a double life - spying at night on Lee Harvey Oswald as the potential assassin within Jake builds. Trailing Oswald takes Jake into the dark side of Dallas, where he realizes Oswald may not be the only threat Kennedy will have to face.

Jake and Bill's partnership starts to struggle as they discover more secrets surrounding the unpredictable Lee Harvey Oswald. The conspiracy involving Oswald deepens, while romance blooms for Jake and Sadie. But by becoming involved with an innocent bystander, has Jake placed his new love in danger?

Everything begins to fall apart as Jake struggles to live two lives: teacher and time traveler. When Sadie's life is threatened, Jake has to make a terrible choice, leaving Bill to his own devices. Lee Harvey Oswald takes steps that will lead him into a date with destiny.

The end is near, and Jake is not up to the task. Sadie scrambles to pick up the pieces, but no one knows the mission as well as Jake. Kennedy and the assassin are on a collision path - but has Jake changed things enough in the past to alter the course of events? The days are counting down as 11.22.63 draws near.

The past pulls out every weapon it has to keep Jake from reaching Dealey Plaza in time to save Kennedy. If he fails, it could mean death for Jake or others close to him - and if he succeeds, it could create a world in which he loses everything he's ever known. What is the cost of doing the right thing?