Henry De Tamble is a young man with a singular disease that makes living life at all, let alone a normal one, difficult. Henry suffers from Chrono-Displacement Order, a disease that is constantly whisking him away from his life to deposit him in the past and future without a moment's notice or control. Unable to travel with money or even clothing, Henry's life is one of uncertainty and danger. But throughout his life, one thing remains constant: Clare Abshire, an heiress who has known Henry since her early childhood when his future self came to visit her: his future wife. They struggle throughout their lives to be together, to maintain a relationship when Henry has no control over his whereabouts. Claire falls in love as a young girl with an older Henry who has known her for many years, but when she meets him in her twenties, he is her age and has never met her before. She begins a relationship with a younger Henry who has yet to become the man she has fallen in love with, just as an older Henry spends his time caring for a young Claire who is alone in the cold atmosphere of her family's home, but is not the woman he leaves behind when he comes to "visit".
They cannot reveal Henry's illness for fear of his being locked up in a mental institution or taken away for study, so they tell few people. Other people weave in and out of the story: his violinist father, who has become an alcoholic recluse since his mother's death in a car accident when Henry was a young boy (a scene he revisits against his wishes). The housekeeper who helped to raise Henry when his father withdrew. Claire's bohemian friends who wonder and even disapprove of her husband who seems dark and even violent to them.
Claire and Henry go through an agonizing process trying to conceive, something Henry is hesitant about for fear of passing on his gift/curse. He goes so far as to have a vasectomy, but a past self comes along and helps Claire to conceive. A daughter is born, and the baby helps to reintegrate Henry's father into their lives. Henry meets with a doctor that he is able to convince of his disease and they go about studying it, they are never able to halt it, but they are able to identify the gene in Henry that they believe makes his time-travel possible.
Now knowing when he dies, and that it is soon, he gathers all his friends and family for a big party, saying goodbye without telling them, then he sits in Claire's arms and spends his last minutes with her. He disappears and then comes back seemingly moments later, fatally wounded.
Claire is despondent but she lives for the few times that Henry has traveled to the future and thus will still be in her life. He visits a couple of times, but he sees their daughter more than her. He promises her that he will come for her on the day she dies. Claire spends the rest of her life, and she has spent it thus far, waiting for Henry.
