Cal Stephanides, "the most famous hermaphrodite in history" (1.2.1), tells us the story of his life, the life of his parents, and the life of his grandparents.
His grandparents, Lefty and Desdemona, are brother and sister in Greece (your read that right: brother and sister). When Greece is attacked by the Turks (maybe someone was upset about that They Might Be Giants song), Lefty and Desdemona flee to America. There, they live with their cousin Sourmelina and her husband, Jimmy Zizmo. After a brief stint as a cog in Henry Ford's factory, Lefty helps Jimmy smuggle liquor into Canada while Desdemona weaves silks for the Nation of Islam. They make the Great Depression seem like a grand old time.
Lefty and Desdemona have two children, but we really only learn much about Milton, who will be Cal's father. Milton is courting his cousin, Tessie (Sourmelina's daughter), but ends up going off to fight in World War II. Tessie almost marries a priest, but Milton returns not in a casket, so Tessie marries him instead. The priest, Father Mike, marries Milton's sister Zoë. They pop out four kids and Mike regrets his entire life while Zoë drinks and shouts a lot. Now that's a great depression.
Milton and Tessie have two kids: one who is just called Chapter Eleven, and Cal. That's right: Finally, we get to Cal's story. Cal is born intersex but raised female, as Calliope, because of her ambiguous genitalia. As Calliope, she spends a lot of time hanging out with her grandfather (Lefty) who has a stroke and soon dies. Then, the Detroit race riots happen, and Milton buses Calliope to private school so she won't have to integrate. Oh the horrors!
When Calliope hits puberty, she starts looking more and more masculine. She also falls in love with a girl whom is referred to as the Obscure Object. Calliope has a sexual experience with both the Object and her brother, and they're both combinations of pleasure and pain… like eating a habañero pepper.
When the Object's brother catches Calliope and his sister together, Calliope runs… smack into a tractor and gets injured. The doctors in the emergency room realize that her genitals are different from other girls', so they send the poor kid off to a specialist in New York, Dr. Luce. Luce suggests sex reassignment surgery to make Calliope a girl, since she was raised as one, but Calliope runs away.
Calliope no more, Cal hitchhikes to San Francisco. There, he finds himself in a sex show run by a man named Bob Presto. Cal swims naked in a pool while people watch him through a peephole. Meanwhile, back in Detroit, Father Mike blackmails Milton, saying that he's holding Calliope hostage. Milton chases Mike down, but dies in a car accident.
The sex show is busted by the police and Cal returns home. He reunites with his family, mourns his father, and looks forward to the future in his new identity.