Augie March grows up with his brothers Simon and George and their single mother (Mama) in a working-class neighborhood of Chicago. The March family’s boarder, Grandma Lausch, establishes herself early in Augie’s childhood as the matriarch of the family. It’s she who teaches Simon and Augie how to make the most of the charitable services they receive, and she encourages both boys to aspire to wealth and status. (She is affectionate toward Georgie, too, but because he has an intellectual disability, she doesn’t have as high hopes for him.)
Both Augie and Simon work odd jobs (secured for them by Grandma) to help support the family. From an early age, Simon is driven, but Augie takes a more laid-back approach to life. When he has a job for a person he likes—like the summer he helps Mama’s cousin-in-law Hyman Coblin with his newspaper delivery business—he works hard. But left to his own devices, he’d rather run around with his friends Jimmy Klein and Clem Tambow than apply himself at work or school. As Simon transitions from school to work, his life and Augie’s begin to diverge. And the family changes forever when Grandma Lausch forces Mama to institutionalize George.
In high school, Augie goes to work for a quadriplegic businessman named William Einhorn. Einhorn becomes a surrogate father figure for Augie, who reveres him and avidly listens to his advice. Soon, Augie is deeply involved in many of the Einhorn family’s affairs. He tags along when Einhorn’s younger half-brother Dingbat unsuccessfully tries to start a career as a boxing promoter. As he graduates from high school, many things change in his life: Grandma Lausch’s sons place her in an institution, Einhorn’s father (the Commissioner) dies, and the Great Depression wipes out much of Einhorn’s wealth.
A job selling shoes at a downtown department store brings Augie to the attention of Mr. Renling, who owns a sporting-goods store in Evanston, a wealthy suburb just north of Chicago. Mr. Renling not only offers Augie a well-paid job, but he and Mrs. Renling unofficially adopt Augie. While accompanying Mrs. Renling on a vacation in Benton Harbor, Michigan, Augie develops a crush on a wealthy young woman named Esther Finchel. Crushingly, Esther refuses to have anything to do with Augie, but her sister Thea finds Augie attractive. She promises they’ll meet again.
When the Renlings try to officially adopt Augie, he breaks away from them, since he’s not willing to renounce his real family. He goes through a rough patch looking for another job, however, and nearly ends up on the wrong side of the law when an old associate named Joe Gorman asks him to help smuggle illegal immigrants across the U.S.-Canada border. The trip goes badly and ends with Gorman being arrested and the penniless Augie having to ride the rails back to Chicago like a hobo.
Back in the city, Augie finds himself solely responsible for Mama. Simon, burned by love after his girlfriend Cissy married another, more financially successful man, has all but disappeared. Augie works at an upscale doggy daycare for a while, until he runs into an old friend (Manny Padilla) who teaches him how to shoplift expensive books that can be sold on the student black market at the University of Chicago. This is how Augie is making a living when Simon suddenly reappears. He’s gotten his life back on track and is, in fact, about to marry Charlotte Magnus, the daughter of a wealthy and well-connected Chicago family. Poised on the verge of success, Simon wants Augie to follow in his footsteps. He introduces Augie to the Magnuses. Augie soon starts working for Simon and dating Charlotte’s cousin Lucy.
But when Augie’s friend Mimi asks him to help her obtain an abortion (her boyfriend, Hooker Frazer, has skipped town) the Magnuses catch wind of it from an associate of the abortionist. Abortions are illegal and dangerous, and no one believes Augie when he claims that the child isn’t his. The Magnuses and Simon repudiate him.
Cut off from Simon’s support, Augie eventually finds work as a labor organizer for the CIO. This is where he meets Sophie Geratis, a hotel maid who becomes his lover. He’s having a good time with Sophie and is starting to become genuinely interested in the organizing work when Thea Fenchel reappears. In the process of divorcing her fabulously rich husband, Smitty, Thea hired private detectives to find Augie. She’s been in love with him since they met as teenagers, she says. Flattered and intrigued, Augie drops Sophie and attaches himself to Thea.
Thea brings Augie to Mexico, where she plans to train an American eagle (which Augie names Caligula) to hunt iguanas. Unfortunately, Caligula is a flop, and Augie and Thea start drifting apart when she starts hunting venomous snakes instead and he spends his time drinking and playing cards with other American expats. Their relationship crashes to a halt when Augie has sex with an American woman named Stella, whom Augie is helping escape her dangerous lover, Oliver.
Heartbroken by his breakup with Thea, Augie goes home to Chicago, where he falls back into his old life. He moves back into his old boarding house, makes peace with Simon, and starts taking classes in the education department at the University of Chicago. He decides that he wants to use his education to open an institution that’s one part farm, one part school, one part foster home. But then WWII breaks out, and Augie joins the Merchant Marines.
In New York City for training, Augie reacquaints himself—and immediately falls in love—with Stella. They get married just before Augie ships out for his first tour of duty. Two weeks in, his ship sinks thanks to an enemy torpedo, and Augie finds himself adrift at sea with the ship’s carpenter (and amateur mad scientist) Hymie Basteshaw. Luckily, they’re rescued by a British ship.
After the war, Augie and Stella settle in Paris. Stella is an actress and Augie is a business associate of an Armenian American lawyer named Mintouchian, who is involved in questionable dealings. Augie’s dream of the foster school has fallen by the wayside, since Stella—who also has a much more complicated past life than Augie expected—is focused on her acting career. But he’s still hopeful that the future will bring him good things.