A young, nameless nightclub comedian (Warren Beatty) living in Detroit lives extravagantly. He has a tryst with a mysterious young woman (Donna Michelle) and accumulates a number of large gambling debts. After a talk with his manager Ruby Lapp (Franchot Tone) who implies to the comedian that he is in trouble, but refuses to tell any information at why, the comedian worries about his own well being.Certain that the underworld syndicate that controls his debts and the clubs where he works is going to punish him, the comedian flees from the nightclub where he is performing, burns all of his ID cards, and hops on a passing freight train and becomes a "boxcar tramp". After several days of living "on the rails" the comedian eventually winds up on the west side of Chicago and living in the streets as a homeless derelict. The man has a free meal of watery soup at a rescue mission where he is read Bible quotes from a stuttering Evangelist preacher (Norman Gottschalk).One day, the former comedian witnesses a small group of homeless men beating up and stealing the shoes, clothing and wallet of another drunken, half-dead homeless bum. The former comedian follows the group and takes, among other things, a social security card with the name Miklos Wunejeva the group of homeless men took off the homeless bum. Using the stolen Social Security card, the former comedian uses it to register for a job at a local employment office, called Rent-A-Man, and soon gets a job in the kitchen of a seedy restaurant at hauling garbage. The nameless man assumes the shortened name of 'Mickey One' to simplify the ethnic Polish name off the stolen Social Security card. Mickey eventually saves up enough money from his low wages to rent a room at a local flop house and buy some new clothes for himself. When a young waitress at the diner named Helen (Jeri Jensen) shows an interest in him, Mickey refuses to get involved with her in any way from being a platonic friend to a lover.Some months later, wanting to resume his career as a stand up comedian, Mickey One contacts an agent, named George Berson (Teddy Hart), who books him several gigs at various nightclubs around the south side. Eventually, Mickey comes to the attention of Ed Castle (Hurd Hatfield) the owner of the posh Club Xanadu who wants to book Mickey.Meanwhile, Mickey's landlady attempts to evict him and move another tenant, a young woman named Jenny Drayton (Alexandra Stewart), into his apartment. Mickey refuses to leave, but Jenny refuses to leave. They eventually decide to live together as a couple and they both fall in love with each other.One night, Mickey and Jenny watch an artist (Kamatari Fujiwara), whom Mickey has seen around town, unveil a kinetic sculpture which goes out of control, explodes, and burns down.At an arcade one evening, Mickey watches a softcore loop film and discovers that the young woman in the porn loop is the same mysterious woman that he had a romantic tryst with prior to him fleeting Detroit.Mickey is wary of the Xanadu booking, fearful that Castle may know his enemies in the syndicate. Mickey is persuaded by Castle to audition for a man connected with clubs in the Midwest, but, fearful that the man might be a mobster and unable to perform without an audience, Mickey cuts his performance short and flees. He confides in Jenny about his plight who then relays it to Castle. Mickey then meets with Castle at his office to tell him that he does not want the gig to perform at his club because of his past connections in Detroit and eventually tells him (and Jenny too) about his last meeting with Ruby Lapp who informed Mickey about his gambling debts. Castle tells Mickey that Ruby Lapp was found murdered weeks earlier back in Detroit, which makes Mickey more frightened about him being a marked man.Determined to contact someone in the syndicate, Mickey searches for the mob-run "crap game", but he is beaten in a brawl involving costumed doormen from various clubs. After he discovers that Berson has disappeared without a trace and his office is ransacked, Mickey decides to keep his commitment to Castle and begins his first show at the club. The film ends with Mickey on stage at Club Xandau performing to the crowd and playing the piano while the scene dissolves from the confined stage to that of the skyline of downtown Chicago.