In Oklahoma during the Great Depression, drought and dust storms—the Dust Bowl—have ruined farmers’ crops and destroyed livelihoods already damaged by the failing economy. Tom Joad is a young man from a farming family who has just been paroled from prison, after serving four years on a homicide charge. As Tom returns home, he meets Jim Casy, an ex-preacher whom Tom knew as a child. Casy no longer preaches of virtue and sin, and instead holds the unity and equality of human spirit as his highest ideal. Together, Tom and Casy travel back to the Joad homestead, but discover that it has been abandoned. Muley Graves, a neighbor who has stayed behind, explains to the two men that the farming families have all been evicted by the landowners and the banks, who have repossessed their land and now use tractors to cultivate it. Muley tells the men that they can find Tom’s family at the home of Uncle John, the brother of Tom’s father, Pa Joad.
When Tom and Casy arrive at Uncle John’s, they find the Joads loading up a car in preparation to leave for California. Pa Joad reveals that the family saw fruit-picking jobs advertised on handbills, and they are heading west to take advantage of these opportunities. Once on the road, the Joads befriend a migrant couple, Ivy and Sairy Wilson, and shortly thereafter, the cantankerous Grampa Joad dies of a stroke. The Wilsons travel with the Joads until the California border, where Sairy becomes too ill to continue. Noah, Tom’s older brother, abandons the family at this border, choosing instead to subsist on his own.
On their way to California, the Joads receive disheartening reports about a lack of jobs and hostility towards “Okies” in California. Once the family arrives in the state, these rumors prove to be true, and their hardships continue. Granma Joad dies during the family’s passage through the Mojave desert. The family is forced to inhabit a Hooverville, a squalid tent city (named after President Herbert Hoover) where migrants live at the whim of unscrupulous contractors and corrupt deputies. At this camp, Connie Rivers—the husband of Tom’s pregnant sister, Rose of Sharon—abandons the Joads. When Tom and a friend from the Hooverville try to negotiate better wages from a contractor, they get into a tussle with a deputy. Tom flees and Casy willingly takes the blame for the fight; the preacher is arrested and taken into custody.
The Joads leave the Hooverville and find refuge at a more comfortable, government-run camp. Instead of a police presence, the camp is governed by a committee elected by the migrants themselves. At this camp, the Joads find some comfort and friendship, but only Tom can find work. One day, Tom discovers that the greedy Farmers’ Association, working in tandem with corrupt deputies, plans to start a riot at an upcoming dance. This will give the deputies a pretense to destroy the camp, which will weaken the laborers’ bargaining power. However, Tom and some other men discreetly pre-empt this attack, and the camp is saved.
The Joads are unable to survive on the income they receive at the camp. They leave to find work elsewhere, and come across a peach-picking compound, where they are brought in to work while other migrants are on strike outside the gates. Tom discovers that Casy is the one responsible for organizing the strike. Just after Tom reunites with Casy, police find them, and one of the officers kills Casy with a pickaxe in front of Tom. In response, Tom kills the officer, and goes into hiding.
The Joads leave to pick cotton and live out of a boxcar, while Tom hides in the wilderness nearby. The family has enough money to eat fairly well, and Tom’s younger brother Al has gotten engaged to the daughter of their housemates, the Wainwrights. Suddenly, torrential rains come, and the Joads are forced to stay in the boxcar (as opposed to go to a hospital or find a midwife) while Rose of Sharon gives birth. Rose of Sharon’s baby is stillborn, and the family flees to a nearby barn to escape the floods. There, they find a boy and his starving father. Ma Joad realizes that Rose of Sharon is lactating, and she gets the rest of the family to leave while Rose of Sharon breastfeeds the starving man.