Tom Joad makes his way home to Sallisaw, Oklahoma by hitchhiking his way there. He has just spent four years in the McAlester State Penitentiary after killing a man with a shovel. He is on parole because he's been a good while in prison. As he approaches his homeland, he comes across Reverend Jim Casy, his childhood preacher. Casy is not a preacher anymore and tells Tom about all of the lecherous things he did when he was a reverend.
The two men make their way to the old Joad farm, only to discover that it's completely abandoned. We're talking not a doily in sight. Muley Graves, an old family friend, stops by. He's a little creepy and looks like a man who has lived all by himself on a desert island for ten years. Muley shares his rabbit, and the three dine famously.
Muley gives Tom and Casy the lowdown. The tenant farmers (people who cultivate someone else's land, giving the landowner a share of the crops) have been forced off of the land by the landowners (i.e., the banks). The drought has made the land dry up, and the dust storm has made farming nearly impossible. There's no money to be had in the farming business. The economy is a mess (thanks to the stock market crash of 1929), and the landowners have realized that one tractor can do the work of an entire family and requires less money to operate and maintain. So the landowners have forced tenant farmers off of the land and out of their homes. Families have gathered all of their belongings, have vacated their homes (homes that have been in their families for generations), and have begun to move west to California. It is rumored that there is lots of space and plenty of jobs out west.
Muley tells Tom that the Joad family is currently staying at Uncle John Joad's house and that they are planning to move west pretty soon, too. Muley's own family left town a long while ago, but he didn't follow them. He couldn't bear the idea of letting the landowners win. So, he lives the life of a vagrant, sleeping in abandoned homes and in riverbeds, making it his life's work to annoy the landowners and their minions. Tom, Casy, and Muley dive into the cornfields when they see a car approach their campfire. The landowner-minions have arrived to see who is trespassing. They search the house and flood the corn rows with light, but to no avail.
The next morning, Tom and Casy walk to Uncle John Joad's house. Lots of hootin' and hollerin' occur when the Joad's realize that their boy has come home at last. Tom is reunited with his mother (Ma Joad), his father (Pa Joad), his grandfather (Grampa), his grandmother (Granma), his brother Noah, his brother Al, his sister Rose of Sharon, his sister's husband Connie, his little brother Winfield, and his little sister Ruthie. Ma Joad is especially moved. She cooks up a delicious breakfast for everyone.
The Joads get ready for their trip. They pack up their car, a Jalopy, with their most essential possessions, and they sell the rest for $18 in town. When everything is packed a ready to go, Grampa realizes he wants to stay behind. He tells everyone he won't leave his home, and so they put four doses of sleepytime cough medicine in his coffee, and then they carry him to the car.
It's not pleasant going. The only people protected from the sun are the three people in the driver and shotgun seats. Everyone else has to ride on top of the car, fully exposed to the sun. On the first day, one of their dogs gets run over by a car. It's pretty sad.
The Joads meet a couple who've set up camp on the side of the road, Ivy and Sairy Wilson. The Wilsons let Grampa take a nap in their tent, because he's acting strangely. Grampa dies soon after of a stroke, and the men bury him in a really deep grave. Touched by each other's kindness, the Wilsons and Joads join forces, and the two families decide to caravan their way to California.
On the third day, the Wilsons' car breaks down. Tom and Al are master mechanics and realize that they need a new part in order to fix the car. Tom suggests that the families go on ahead without him and the preacher, and that they will stay behind and get the car fixed. Ma Joad refuses to leave anyone behind. And so the Joads go find a campsite down the road where they can chill (because Granma is not well) while Tom, Al, and the preacher stay and fix the broken car.
It doesn't take long for Tom and Al to fix the car, and they catch up with their family at a campsite whose owner charges people 50 cents a day to camp there. That's a lot of money when you only have $40 bucks to get you to California. A bunch of men are hanging out on the steps of the campsite owner's house. One man tells everyone that he's on his way back from California. He says that it's miserable out west, and that there aren't any jobs. Tom and Pa Joad are freaked out, but they decide not to worry about it too much.
The Joads keep on truckin', going over the New Mexico mountains and through Arizona on Route 66. They see lots and lots of cars going west, but very few cars coming east. When they cross the California border, they stop at a campsite in Needles, CA by the Colorado River. Because they have to get across the sweltering hot desert (that would be the Mojave Desert), the Joads and Wilsons decide to sleep during the day and then drive at night.
The men go swimming in the cool river, and encounter a father and son who are on their way back from California. The father and son tell the Joads that life is bitter in California – there are no jobs to be had, and the Californians hate the migrant workers. Tom settles down for a nap, and his brother, Noah, tells him that he's not going with the family any further, that he's going to live by the Colorado River. Noah disappears.
Ma Joad looks after Granma. Granma is really sick, and a strange woman (a Jehovite) barges into the Joad tent and tells Ma Joad that Granma's going to die and she would like to assemble a prayer circle around her. Ma Joad says get the h-e-double-hockey-sticks out of our tent, and she sends the woman packing. A policeman stops by the tent to tell Ma that they have to leave, or else. Ma chases him out of the tent, too, with a skillet. Sairy Wilson is nearing death herself, and Ivy Wilson tells the Joads to push on without them. The Joads leave at 4pm, making their way across the Mojave Desert.
Later that night they arrive at a border patrol station, and the guard wants to inspect their truck to make sure they aren't smuggling fruit. Ma pleads with the border patrol to let them go quickly. She says that Granma is really sick. Unbeknownst to the rest of the family, Granma died a few miles back. Ma Joad doesn't want the family to get in trouble for have an dead old lady in their truck.
The Joads push through to Bakersfield, CA. They are awestruck by the beauty of the Californian valley country. After depositing Granma's body at the Bakersfield coroner's office, the Joads find a campsite just out of town. The campsite is called a Hooverville. It's a shady place with lots of half-starved families living in tattered tents and makeshift shacks. Tom and Al make friends with one of the men there who is getting ready to go north to look for jobs. The man, Floyd Knowles, warns them that there are no jobs to be had here and the entire farming system is corrupt. Landowners are paying workers practically nothing, and the law is on their side, too.
A man posing as a contractor arrives at the Hooverville in a shiny car, and he tells the men he has work for them. Floyd demands to see his contracting license and to know how much the man intends to pay the workers. The contractor sets a policeman on Floyd, and Floyd runs away. Tom trips the policeman, the policeman tries to shoot Floyd (but shoots a woman's knuckles off instead), and then Casy kicks the policeman unconscious. More police arrive, and Casy turns himself in, saying goodbye to the Joads. Around the same time, everyone realizes that Connie Rivers (Rose of Sharon's husband) has run away for good – the pregnant Rose of Sharon is a mess, and Uncle John gets drunk.
Tom drives the family south to Weedpatch, a government camp with hot running water, showers, and real toilets. The family is overjoyed to be around decent people, and they stay there for a month. The Joad men can't find steady work, however, and so Tom drives the family to a peach camp where pickers are needed. Here, the landowners are paying pickers five cents for every bushel of peaches picked. The Joads pick tirelessly and eat a delicious meal that night of hamburgers. There are picketers outside of the peach camp, and Tom sneaks out that night to find out why they are picketing.
Tom encounters Reverend Casy in tent not far down the road. The two exchange stories, and Casy tells Tom he and his buddies have been picketing low wages, trying to get landowners to treat workers fairly. The men hear footsteps and realize that they are being pursued. Casy and Tom escape along the creek, but they are soon caught by the authorities. Someone drives a pick axe into Casy's head. Tom's nose gets broken and his cheek is torn. He takes the pick axe from Casy's head and drives it into the man who killed Casy. Tom sneaks back to the peach camp and must hide throughout the next day.
The Joads sneak Tom out of the peach camp nestled between two mattresses. Tom decides to separate from his family and to live in the bushes while they look for work picking cotton. The Joad family sets up camp near an abandoned boxcar. Not much later, twelve-year-old Ruthie Joad gets into a fight and tells her bully that her brother has killed two men already and could kill the bully's brother, too. Ma finds Tom to tell him that the word is out and that he is in danger. Ma and Tom say goodbye to one another.
The winter rains come, and the creek near the abandoned boxcars starts to rise. Rose of Sharon goes into labor. Pa convinces a bunch of men to help him build troughs to keep the creek water from rising too quickly, but they are no match for the flood. Rose of Sharon's baby is still-born. The waters continue to rise until they flood the boxcars. The Joads build a platform to keep themselves dry.
Ma, Pa, Rose of Sharon, Ruthie, and Winfield decide to leave the boxcar (where Al will remain with his new fiancée, Aggie, and her parents, the Wainwrights), and they go in search of a dry shelter. They come across an abandoned barn. Inside a little boy is sitting next to his half-starved father who has been feeding his son instead of feeding himself. Rose of Sharon asks everyone to leave the barn, and she lies down next to the half-starved man, letting him drink her breast milk.