At the beginning of The Grapes of Wrath by John Steinbeck, we see a man walking along the highway. He gets a ride from a trucker, who starts asking about the stranger's past. We learn that the stranger is Tom Joad, who is traveling to his family's 40 acre farm. We also learn that Tom has been in jail, serving four years of his seven year sentence for manslaughter, but got out for good behavior.

Tom begins to walk down the road to his family's ranch. He then meets up with Jim Casy, who was sitting under a tree on the side of the road. Casy was a preacher, but gave it up because he believes that every man is holy, so there is no need to preach. Casy joins Tom on his way to his family's farm, after Tom tells him of his run in with the law. When they arrive at the house, they find it to be desolate. The house has been pushed in on one side, and the well is dry. They then see Muley Graves, a neighbor, coming down the road. Muley tells them that his family has moved in with John Joad, Tom's uncle.

The next day, Jim and Tom walk to John's house. When they arrive, they see that the family is about to move. Tom is greeted by his family, who each ask him if he had broken out of prison. After they have breakfast, Uncle John and Ruthie and Winfield, Tom's two younger siblings, leave to sell some of what they have for money. Al then arrives, and is reunited with his brother, who he has come to idolize somewhat.

The family prepares to leave at dawn the next day. They slaughter the two pigs that remain, and salt the meat. Ma sifts through her souvenirs, saving what little she can, and tossing the rest of it into a fire. They have to drug Grampa to get him to leave, and give Muley Graves their dogs, and give him some chickens, too. They start on their way to California, but before long, they stop at a gas station. A dog gets hit by a passing car, and Rose of Sharon becomes frightened of the effect it has on her child. The gas station attendant promises to bury the dog, and the family leaves.

Later that day, Tom pulls over so that they can have dinner. They settle down next to another family, the Wilsons, who are having car trouble. Later that evening, Grampa dies of a stroke. The family mourns and buries Grampa. Tom and Al start to work on the Wilson's car later that night. After a few days, they stop by a river in Arizona. A man and his son soon come through, and tell them of the terrible working conditions to be found in California. They also tell the Joads that "Okie" means "dirty song-of-a-bitch". Granma starts to lose her mind, and Noah decides to leave the family. The Joads and the Wilsons separate. The Joads continue on their journey. They pass the border, after being stopped by a guard. When they stop driving later that morning, Ma tells the family that Granma died overnight.

After they leave Granma's body at the county coroner's office, they drive to the edge of town, to a small and dirty settlement. A man explains to them that anyone who tries to organize the settlers in protest of the small wages is arrested. Rose of Sharon and her husband, Connie, have a slight argument, and Connie leaves. Tom trips a deputy, and Casy accepts the blame, since Tom is still on parole. The family leaves the dirty camp, and arrives at a government camp, arriving just after a spot opens up. There, Tom gets some temporary work.

After five or six days, the family must leave. They have heard of work, and go there to start earning money. They are "greeted" by some police, who escort them to the peach fields. There, they learn that they will get paid five cents a box. By the end of the day, they have earned a dollar. Ma spends all of the money on a measly dinner. Tom goes out, and finds Jim Casy, who tells him that he is trying to organize the people. Two officers come along, and kill Casy. Tom kills one of them, and his struck in the face by the other. He hides, after telling his family of some work nearby.

The Joads make a good amount of money picking cotton, as they are some of the first to arrive, and get a boxcar to live in. Ma goes to see Tom, who is hiding in a cave. Tom decides he will dedicate his life to organizing the people, even though it is dangerous. On her way back to the family, Ma is told of some work. When she gets back, Al announces that he is going to marry Agnes, daughter of the family that the Joads share the boxcar with. The next day, all of the work has been done, and it starts to rain. The next day it starts to flood. The men try to build a dam, but a floating tree punctures it, and the boxcar begins to flood. Rose of Sharon goes into labor, and gives birth to her child, who is stillborn.

A few days later, most of the family goes out in search of a dry place to stay. They come upon a barn, and a boy and a sick man. The man must have some soup or bread. The book ends with Rose of Sharon giving the man some of her breast milk.