The novel centers around Henry DeTamble, a man with a rare genetic disorder that causes him to involuntarily time travel at random intervals. He has no control over when or where he travels through time. The story is narrated from the alternating perspectives of Henry and his wife Clare Abshire. Clare first encounters Henry when she is six years old in 1977, as Henry has time-traveled from the future. Over the years, Henry continues to visit Clare sporadically throughout her childhood and adolescence, creating a deep connection between them.

When Clare is 20 years old in 1991, she meets Henry for the first time from his perspective at the Newberry Library in Chicago. Despite not knowing her yet, Henry is drawn to Clare, who is already in love with him due to their shared history from her childhood encounters with his time-traveling self.

The story unfolds in a non-linear fashion, reflecting Henry's disjointed experience of time. Clare and Henry eventually marry, but their relationship is constantly challenged by Henry's unpredictable disappearances into the past or future. Henry often returns from his time travels injured, disoriented, and naked, as he cannot travel with belongings.

Throughout their marriage, Clare and Henry grapple with the complexities of Henry's condition, including its impact on their attempts to have children.

Despite the difficulties posed by Henry's time traveling, their profound love for each other remains a constant, as they navigate the paradoxes and heartbreaks that arise from Henry's unique existence outside of linear time.

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