The narrative begins just after Tom Joad is paroled from McAlester prison, where he had been incarcerated after being convicted of homicide in self-defense. While hitchhiking to his home near Sallisaw, Oklahoma, Tom meets former preacher Jim Casy, whom he remembers from his childhood, and the two travel together. Arriving at Tom's childhood farm home, they find it deserted. Disconcerted and confused, Tom and Casy meet an old neighbor, Muley Graves, who says the family is at Uncle John Joad's home nearby. Graves says the banks have evicted all the farmers. They have moved away, but Muley refuses to leave the area.
The next morning, Tom and Casy go to Uncle John's. Tom's family is loading their remaining possessions into a Hudson sedan converted into a truck; with the crops destroyed by the Dust Bowl, the family has defaulted on their bank loans and their farm has been repossessed. The family sees no option but to seek work in California, which has been described in handbills as fruitful and offering high pay. The Joads put everything they have into making the journey. Although leaving Oklahoma violates his parole, Tom takes the risk, and invites Casy to join the family.
Traveling west on Route 66, the Joads find the road crowded with other migrants. In makeshift camps, they hear many stories from others, some returning from California. The group worries that California may not be as rewarding as suggested. The family dwindles on the way: Grampa dies and they bury him in a field; Granma dies close to the California state line; and both Noah (the eldest Joad son) and Connie Rivers (the husband of the pregnant Joad daughter, Rose of Sharon) leave the family. Led by Ma, the remaining members continue on, as nothing is left for them in Oklahoma.
Reaching California, they find the state oversupplied with labor; wages are low, and workers are exploited to the point of starvation. The big corporate farmers are in collusion and smaller farmers suffer from collapsing prices. All police and state law enforcement authorities are allied with the growers. At the first migrant Hooverville camp the Joads stop at, Casy is arrested for knocking down a deputy sheriff who is about to shoot a fleeing worker for alerting others that the labor recruiter, travelling with the officer, will not pay the wages he is promising. Weedpatch Camp, one of the clean, utility-supplied camps operated by the Resettlement Administration, a New Deal agency, offers better conditions but does not have enough resources to care for all the needy families, and it does not provide work or food. Nonetheless, as a Federal facility, the camp protects the migrants from harassment by local deputies.
How can you frighten a man whose hunger is not only in his own cramped stomach but in the wretched bellies of his children? You can't scare him – he has known a fear beyond every other.
—Chapter 19
In response to the exploitation, Casy becomes a labor organizer and tries to recruit for a labor union. The Joads find work as strikebreakers in a peach orchard. After picking for most of the day, they are only paid enough to buy food for that night's supper and some for the next day. The next morning the peach plantation announces that the pay rate for the picked fruit has been reduced by half. Casy is involved in a strike that turns violent. When Tom witnesses Casy being struck and killed with a pickaxe, he kills the attacker and takes flight. The Joads quietly leave the orchard to work at a cotton farm where Tom risks being arrested, and possibly lynched, for the homicide.
Knowing he must leave to avoid capture and protect his family from being blacklisted from working, Tom bids his mother farewell and vows to work for the oppressed. The family continues to pick cotton and pool their daily wages to buy food. Upon its birth, Rose of Sharon's baby is stillborn. Ma Joad remains steadfast and forces the family through the bereavement. With the winter rains, the Joads' dwelling is flooded and the car disabled, and they move to higher ground. In the final chapter of the book, the family takes shelter from the flood in an old barn. Inside they find a young boy and his father, who is dying of starvation. Ma realizes there is only one way to save the man. She looks at Rose of Sharon and a silent understanding passes between them. Rose of Sharon, left alone with the man, goes to him and has him drink her breast milk.
