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The narrative begins just after Tom Joad is paroled from McAlester prison for homicide. On his journey to his home near Sallisaw, Oklahoma, Tom meets former preacher Jim Casy, whom he remembers from his childhood, and the two travel together. When they arrive at Tom's childhood farm home, they find it deserted. Disconcerted and confused, Tom and Casy meet their old neighbor, Muley Graves, who tells them the family has gone to stay at Uncle John Joad's home nearby. Graves goes on to tell them that the banks have evicted all the farmers off their land, but he refuses to leave the area.
Tom and Casy get up the next morning to go to Uncle John's. There, Tom finds his family loading a converted Hudson truck with what remains of their possessions; the crops were destroyed in the Dust Bowl and, as a result, the family had to default on their loans. With their farm repossessed, the Joads cling to hope, mostly in the form of handbills distributed everywhere in Sallisaw, Oklahoma, describing the fruitful state of California and the high pay to be had there. The Joads are seduced by this advertising and invest everything they have into the journey. Although leaving Oklahoma would be breaking parole, Tom decides it is a risk worth taking. Casy is invited to join the family as well.
Going west on Route 66, the Joad family discovers the road is saturated with other families making the same trek, ensnared by the same promise. In makeshift camps, they hear many stories from others, some coming back from California, and are forced to confront the possibility that their prospects may not be what they hoped. Along the road, Grampa dies and is buried in a field; Granma dies close to the California state line, both Noah (the eldest Joad son) and Connie (the husband of the pregnant Joad daughter, Rose of Sharon) split from the family; the remaining members, led by Ma, realize they have no choice but to go on, as there is nothing remaining for them in Oklahoma.
Upon arrival, they find little hope of making a decent wage, as there is an oversupply of labor, a lack of laborers' rights, and the big corporate farmers are in collusion, while smaller farmers are suffering from collapsing prices. A gleam of hope is presented at Weedpatch Camp, one of the clean, utility-supplied camps operated by the Resettlement Administration, a New Deal agency that has been established to help the migrants, but there is not enough money and space to care for all of the needy. As a Federal facility, the camp is also off-limits to California deputies who constantly harass and provoke the newcomers.
|“||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 of laborers, there are people who attempt to organize the workers to join a labor union, including Casy, who had gone to jail after taking the blame for attacking a rogue deputy. The remaining Joads work as strikebreakers on a peach orchard where Casy is involved in a strike that eventually turns violent. Tom Joad witnesses Casy's killing and kills the attacker, becoming a fugitive. The Joads later leave the orchard for a cotton farm, where Tom is at risk of being identified for the murder he committed.
He bids farewell to his mother, promising that no matter where he runs, he will be a tireless advocate for the oppressed. Rose of Sharon's baby is stillborn; however, Ma Joad remains steadfast and forces the family through the bereavement. When the rains arrive, the Joads' dwelling is flooded, and they move to higher ground.