After the Joads along with Jim Casy leave for California, the scavengers from town come to take from the farm whatever they could use or think would be useful. Soon after, the animals stake their claim to the house, the bats use it as their new cave and the cats use it for shelter during the night. The house slowly begins to deteriorate, because no one cares for it any longer. The man who runs the tractor to plant and till the soil just thinks of it as a place to work, not a living breathing farm.

The people flee down Highway 66. The road takes them through Oklahoma, Texas, New Mexico, Arizona and finally to California. Along the way the travelers hope and pray their vehicles will be able to endure the trials of the road. They hope the cars and trucks with poor tires, leaking radiators, and other various problems can get through the heat and mountains to reach the supposed promise land of California. They are not always welcome by those they encounter along the way. The men who run the service shops and tire stores try to receive as much money for their goods as they can. They have no compassion for the plight of the people trying to reach California, after all they have to make a living and support their families. California does not seem to want all these people, because the promised jobs are quickly being filled and then what will happen to the rest who cannot find employment.

The Joads are traveling down Highway 66 through Oklahoma City and on their way to the state border. They realize the gallon of drinking water they meant to bring along was left behind. This causes concern for the family because the water was not only for drinking, but to also fill up the radiator if it needed extra water. They stop at a small decrepit gas station to fill up the radiator, get some gas, and drink some water. Grampa is still in a haze, because of the medicine he was given to make him sleep through the trip. While at the gas station, the dog gets away from the family and is run over by a car. This causes some distress for the family and is another complication in the trip. Ma is also concerned about Tom crossing the state line, because her husband has told her it would violate Tom's probation. Tom tells her as long as he does not commit a crime, everything will be alright.

After riding for a while, Ma Joad suggests to Tom it might be time to find a place to pull over, to camp for the night. He sees a car pulled over in a culvert with a tent pitched and decides it would be a good place to stop. They meet Ivy and Sairy Wilson from Kansas whose car has broken down. While there Grampa becomes very ill and has a stroke. He dies from the stroke. The family decides to bury him by the roadside, to save the forty dollars they would have to pay to have him properly buried. The Wilsons help out the Joads, by helping with Grampa and the Joads repay them by fixing their car. After thinking about it, the two families decide it would be better if they traveled together, to complete the trip.

The people of the Western States are nervous about the people like the Joads and Wilsons who are coming to their land and trying to get jobs. They fear the change that all these people will cause to their lives and the nation.

As these travelers cross the county they see signs for roadside restaurants, one of which is run by Mae and Al. Mae likes to keep the truck drivers happy by being fun to talk to, all the while giving them great service. She is amazed by all the cars which have been traveling down her little section of Highway 66. One day a family, in an old 1926 Nash, pulls into the restaurant needing to use the hose in the driveway. Mae allows them to use the hose, but she keeps an eye on them. She has been told by truck drivers, the poor people traveling down 66 often steal from establishments like hers. The father of the family asks Mae if she will sell him a loaf of bread for a dime. She tries to tell him the bread goes for fifteen cents, but the man is persistent in asking for only a dime's worth of bread. Finally, Al tells her to sell the man the bread for a dime. She even goes so far, as to sell the man two pieces of candy for his boys at the price of a penny. The candy actually went for the price of a nickel for each piece. Her kindness is rewarded by the two truckers eating at the counter. Instead of leaving a quarter for their fifteen cent meal, they each leave fifty cents. She is astonished at their generosity. Then she quickly goes back to the daily routine of her and Al's life.

This section of the book is filled with tragedy through the loss of Grampa and the dog. The complications of having left the water behind, but also the hope brought by joining up with Ivy and Sairy Wilson. The Joad family is finding out that life on the road is even harder than they thought it would be.