Tom Joad, on parole from prison, is making his way home.  He bumps into Jim Casy, a former preacher and friend of the family, who joins Tom on his travels.  When the family house comes in sight, it’s evident that it has been abandoned. The arrival of a fellow sharecropper, Muley Graves, clarifies this.  The Dust Bowl that developed in Oklahoma, and the adoption of tractors, has driven the Joads to Tom’s uncle’s house.

Tom and Casy head over to Uncle John’s, where they find the family preparing to leave.  While he’s been away Tom’s younger siblings, Winfield and Ruthie, have grown much bigger, and his sister Rosasharn is married and newly pregnant.  His brother Al has become a young man, experienced with cars; his grandparents are as cantankerous as ever.  Happy to see Tom, the family speed up their preparations to leave.

The road isn’t easy for the Joads; the stress of leaving home causes Grampa Joad to have a stroke and die on their first stop, and losing her husband makes Granma Joad very ill.  The Joads learn that they’re not alone in their emigration from Oklahoma, but once they start to meet families coming back from California, worry and doubt are planted in their minds.  Tom’s older brother, Noah, wanders off to live by the river where he thinks he’ll have a better life than in California.  Granma Joad follows her husband to the grave while crossing the Californian desert.

Their first camp in California proves disastrous: Casy gets arrested protecting Tom after he assaults a deputy. As the family prepares to move on, they discover that Rosasharn’s husband Connie has abandoned her and his unborn child.  A stint in the government-run Weedpatch camp reminds the Joads that kindness still exists, and they settle into a life with friendly people and nice facilities.  The lack of work, however, forces them on and they turn to peach-picking. Tom comes across Casy who has turned to rioting.  After witnessing his killing, Tom attacks the murderer. With telltale injuries, he has to go into hiding.

The final stop for the Joads is the cotton fields of California, where they form part of a community in boxcars.  Rosasharn’s baby is stillborn; rain storms cause the river to flood their camp.  The novel ends as the Joads move to higher ground and find a man more destitute and desperate even than themselves. Rosasharn feeds him with her breastmilk, symbolising her new strength and the hope it represents for the family.