The story of The Human Comedy, including the characters Homer and Ulysses in particular, is based on Saroyan's life, living fatherless with his siblings and his mother. The town in the novel, Ithaca, California, is based on the real town of Fresno, California, Saroyan's hometown.
The book contains several references to Homer's Odyssey, including the use of Homer as the name of the main character in this novel. Homer's young brother's name, Ulysses, is the Roman form of the name Odysseus, the protagonist of Homer's Odyssey. The books share the theme of returning home. Ithaca is both Homer's and Ulysses' hometown in the novel and Odysseus' home island in the Odyssey. The name Helen Eliot (a nod to Homer's Helen of Troy) is used as the name of the girl that Homer loves.
The story occurs during World War II.