Hollywood film director John L. Sullivan dreams of making a film called Brother, Where Art Thou, dealing with the misery of the poverty-stricken, and convinces the studio executives to allow him to do research by traveling cross-country disguised as a hobo.

As "Sully" treads the road dressed in a hobo outfit from the studio costume department, a fully-equipped "land yacht," complete with physician, photographer, reporter, secretary and chauffeur, follows him to take care of his every need.  Hampered by their presence, Sully insists on traveling alone and arranges to meet the land yacht in Las Vegas.

After working as a hired hand for a widow who has more in mind for him than chopping wood, he sneaks out of her house at night and hitchhikes, but the truck he gets a ride with lands him back in Hollywood.  Frustrated by his failure, Sully wanders into a diner to buy a cup of coffee with his last dime, and a beautiful blonde actress, down on her luck, takes pity on him and buys him breakfast.  Sully and "The Girl" are later arrested for stealing his own car, but they return to his palatial home after his valet and butler bail them out.

The Girl dresses as a boy and joins him for his experiment, and the next morning they hop an outbound freight car.  Sully and The Girl live like true hoboes, wandering through shantytowns, lining up for food at soup kitchens and listening to midnight sermons in order to secure beds at missions.  In Kansas City, Sully declares his mission complete, but The Girl saddens at the thought of losing him to Hollywood.  He admits to her that although he cares for her, his greedy wife will not release him from their marriage of convenience, arranged by his business manager to lower his taxes.

That night, Sully wanders the streets handing out $5,000 worth of five-dollar bills to the needy.  A hobo wearing Sully's stolen shoes which contained his only identification, follows Sully and robs him; after knocking him unconscious, he drags the unconscious Sullivan onto a freight car.

The hobo dies shortly thereafter when he is hit by a train, and Sully awakens the next day at an unknown train station.  Disoriented, Sully is arrested after an unintentional altercation with a railroad employee, and because he cannot recall his identity due to the severe blow to his head, he is called "Richard Roe" and sentenced to a hard labor camp.  Sully finally recalls his identity but is beaten by the warden for speaking out of turn.  At work on the chain gang, Sully is befriended by an elderly trustee, who helps him survive.  He is placed in the sweatbox because of his outburst after seeing a front-page article reporting his presumed death.

One evening, the convicts are allowed to see a Mickey Mouse cartoon at a black church.  The parishioners are gracious, and Sully the sophisticate surprises himself when he joins in the uproarious laughter of the audience at the antics on the screen.

In order to get his picture in the newspaper, Sully confesses to his own murder.  The Girl, hard at work on a film, sees his photo in the newspaper and brings it to the attention of the studio heads.  Overjoyed that he is alive, Sully's friends and coworkers meet him after he is released from the labor camp.  Sully is pleased to hear that his wife, believing he was dead, married his business manager immediately, and that he is free to marry The Girl.  Aware of the powerful misery of the poor and disadvantaged, Sully abandons his idea of directing a tragedy and is determined to produce a film that will make people laugh.