Benjamin is born with the physical appearance of a 70-year-old man, already able to speak. His father Roger invites neighborhood boys to play with him and orders him to play with children's toys, but Benjamin only obeys to please his father. At five, Benjamin is sent to kindergarten but is quickly withdrawn after he repeatedly falls asleep during child activities.

When Benjamin turns 12, the Button family realizes that he is aging backward. At the age of 18, Benjamin enrolls in Yale College but having run out of hair dye on the day of registration, is sent home by officials, who think he is a 50-year-old lunatic.

In 1880, Benjamin is 20, his father gives him a control of Roger Button & Co. Wholesale Hardware. He meets Hildegarde Moncrief, a daughter of General Moncrief, and falls in love with her at the first sight. Hildegarde mistakes Benjamin for a 50-year old younger brother of Roger Button, and without realizing the fact of Benjamin's abnormality, the two get married six months later.

Years later, Benjamin's business has been a great success, but his family life hasn't been well for him. Benjamin starts to get tired of Hildegarde because she's a nagging woman that is not longer beautiful as before. His family life is so boring that he joins the Spanish-American War in 1898. He had a great success in the military, ranked up to lieutenant colonel, and rewarded with a medal. He then quits the military because his company requires his care.

In 1910, Benjamin turns over control of his company to his son, Roscoe, and enrolls at Harvard University, having the appearance of a twenty-year-old. His first year at Harvard is a great success, and he is dominant in American football, notably obtaining revenge against Yale for his earlier unpleasant experience. However, by the time Benjamin reaches his last 2 years, he is a weak sixteen-year-old, unable to play football and barely able to cope with the academic load.

After graduation, Benjamin returns home, only to learn his wife has moved to Italy. He lives with Roscoe, who treats him very sternly, making Benjamin call him "Uncle" in front of his house guests. As the years progress, Benjamin turns from a moody teenager into a young child. Eventually Roscoe has a child that later attends kindergarten with Benjamin. After kindergarten, Benjamin slowly begins to lose memory of his earlier life. His memory fades away to the point where he cannot remember anything except his nurse. Then everything fades to darkness.