Sal prepares for another jaunt West with Dean and friends; he wants to go along for the ride, and hopes to have an affair with Marylou in San Francisco. Before they leave, the group stays at Carlo's place for awhile. Carlo tries to ask them all serious questions about what they are doing (and what they have done to Camille, Galatea and Lucille), but gets nothing but giggles for answers. Sal comes in every day and watches the spectacle.
One day, sitting in a bar, a blushing Dean tells Sal he wants Sal to make love to Marylou while Dean watches. Sal knows that it's because Dean wants to see how Marylou would be with another man. He agrees, but when all three of them are lying on the bed together, he can't go through with it. Finally, with Carlo irritated, his apartment a mess, and Dean and Marylou banged up from fighting with each other, the group starts on their trip.
They pass through Washington, D.C., on the day of Harry Truman's second-term inauguration. Ed Dunkel starts driving, and against their instructions, drives recklessly and they are caught and taken in to a police station. The police are suspicious of them, but can't do anything more than charge a $25 fine--leaving them only $15.00 to cross the country. They start picking up hitchhikers to try to get some gas money. Their first hitchhiker is a scraggly Jewish wanderer, who claims to find the Torah in the wilderness, their second a sad boy who lies that he has an aunt who can give them some money.
They pass through South Carolina, Georgia and Florida. Dean steals gas when a station attendant isn't paying attention, and tells them his life story: jumping freight trains with his drunk father, losing his virginity at nine years old. They arrive in drowsy Louisiana and go to Bull Lee's house, a dilapidated house on swampy land outside of town. Jane Lee greets them, high on benzedrine as always. Eccentric writer-junkie Bull Lee greets Sal courteously; Bull and Jane's two kids are running around the yard. Sal describes Bull: a "Kansas minister," a collector of experiences who has worked as an exterminator and traveled around the world, and now spends most of his time experimenting with his drug habit. He is the teacher of their group; Sal and Carlo have both learned from him.
Bull asks them questions about themselves that they can't answer--as usual--and gives them drugs; he considers Dean a madman. Then they go out in New Orleans, and Bull deliberately takes them to the dullest bars to prove that bars aren't what they used to be. It's a foggy, ghostly night. They stay up at Bull's house, everyone with their own project, and Sal goes out, wanting to sit by the Mississippi River. Unfortunately, he has to content himself with looking at the river through a fence.
They spend the next morning immersed in Bull's weird life: picking nails out of a wormy piece of wood, throwing knives at a target, hearing stories of Morocco, and fighting with his neighbors, and then go to a racetrack, where Bull loses money. Back in Bull's backyard, they compete by showing each other athletic tricks: Dean is the fastest. Later, in New Orleans, they go to the railyards and hop on and off freight trains, Dean showing off his brakeman skills.
Ed and Galatea decide to stay in New Orleans. Dean, Sal and Marylou say goodbye to everyone; they're off to California.
It's becoming clearer what Sal has in common with Dean: the ache to be moving, on the road. After they start west again, Sal mentions a collective euphoria: they are leaving "confusion and nonsense" behind to perform their only "noble function": move. The road, to Sal, is "pure" and straightforward as nothing else is in his life. This desperate desire to move is the one thing that binds Sal and Dean closer than anyone else in the novel: Even Carlo Marx can't understand what they're doing. Junkie Bull Lee, who himself leads an exceedingly odd life, considers Dean a "madman" and advises Sal to get away from him. Sal seems to understand Dean better than anyone else. Even when he admits that nothing Dean says makes sense, Sal believes that he understands what Dean means anyway. Dean seems to also consider Sal some kind of alter ego. They trust each other so much that he even asks Sal to sleep with Marylou.
Yet, even as Sal's crazy friends look askance at his close association with Dean. Sal considers everyone and everything he has ever known as "One"--part of the same collective experience. There is a collective restlessness, desperation and craziness which leads sometimes to exhilaration. Kerouac constantly uses the words "sad" and "American" in describing Sal and his friends' experiences, as in: "our sad drama in the American night"--they represent an entire culture, a time. When Sal wants to sit by his much-dreamed of Mississippi River, he can't because there is a fence blocking his access. There is a pervasive sense of something precious having been lost, a deeper sadness underneath the carousing of their group. Sal mentions, the night that they cross the ferry in New Orleans, that a girl committed suicide off the deck. We don't see the tragedy, but we know it happened; similarly, Sal often mentions a deep sadness, but avoids looking at the facts that caused it.
Also in this section, we see more evidence of Kerouac's skill at giving a rounded perspective of Sal and the events. For example, On the Road presents a phallocentric world, with women as largely replaceable accessories, providing either sex, nurture or both. Yet, there is often an anti-glorifying spectator, who allows us to see the men in a less flattering light than they see themselves, as when Dodie, Bull and Jane's daughter, watches the men show off to each other in the backyard: "look at the silly men!" she calls to her mother.