Blues musician Robert Johnson travels to a crossroads in Mississippi, then records his music for a producer in a seedy hotel. Many years later, aspiring blues musician Eugene Martone obsessively researches the life of Robert Johnson. One day, Eugene visits patient Willie Brown at a criminal rest home in New York City, but a nurse says that Willie does not want visitors, and he is turned away. Undaunted, Eugene takes a job as a part-time janitor to gain access and hears the musician play harmonica in his room. Willie wants to be left alone, but Eugene presses him to admit that his stage name was “Blind Dog Fulton” when he was touring from 1939 to 1968. Eugene believes Willie was friends with Robert Johnson, changed his name to Blind Dog and moved to Chicago, Illinois, after Robert’s tragic death, but Willie denies it. A few days later, Eugene reveals that Robert was supposed to record thirty blues songs during his famous Texas sessions, but only twenty-nine exist. Eugene hopes that Willie will help him find the missing song. The fact that Eugene is a blues musician from Long Island, New York, makes Willie laugh. Later, The Juilliard School professor, Dr. Santis, tells Eugene he was accepted to the school as a classical music student, but lacks passion. The professor hints that Eugene is not a blues musician because he was not born into it. Either way, Eugene must choose the course of his musical future. One day, Eugene gives Willie a photograph of Robert Johnson, Willie, and other musicians, then leaves. Willie remembers signing a contract with the devil in the guise of a slick record promoter at a Mississippi crossroads, where Robert told him he would find his fortune as a harmonica player. In the present, Willie continues his needling as Eugene plays the blues on his guitar. Then, Willie admits to being Blind Dog, but contends that Eugene has not "suffered enough" to play the blues. Eugene explains that he can acquire this experience after he graduates from Juilliard, but Willie insists there is no time to waste. When Eugene wants to record the missing song at the rest home, Willie proposes that Eugene help him escape to Fulton’s Point where he has property just outside Yazoo City, Mississippi, and then he will give Robert’s missing song to Eugene. At first, Eugene refuses to bargain, and Willie calls him a coward. Then, Willie shows him the money he has saved, and Eugene agrees to take him to Mississippi. The next day, Eugene and Willie evade an orderly, escape in a taxicab, and board a Greyhound bus, where Willie tells Eugene about his friendship with Robert. Although the men were friends from 1932 to 1938, they parted ways when Willie wanted to go to Chicago, and Robert wanted to return to Mississippi, where he died a few months later. Willie also reveals that he was imprisoned for the shooting death of guitar player, Snooks Jordan. When they reach Memphis, Tennessee, Eugene discovers that there is not enough money for a two-hundred-mile ride to Yazoo City, and the travelers must hitchhike. They do more walking than riding, and even jam a little. When Willie suggests his playing lacks a certain something, Eugene responds that maybe he will go to the crossroads and make his deal with the devil. Willie slaps him in the face. Later, Willie calls Eugene a know-it-all, who plays a beat up guitar because he thinks it makes him look cool. At a music store, Eugene tries out an electric guitar with a portable amplifier worth $400, and they barter Eugene’s $1,100 watch for it. Later, they take shelter from the rain in an abandoned house in the woods where a seventeen-year-old runaway named Frances threatens Willie with a knife. After Willie disarms her, Frances leaves to hitch a ride, and the musicians join her. On their journey, Frances propositions a bar owner named Lloyd, but Eugene does not like the situation and rescues her. However, Frances wants to steal Lloyd’s money before they leave the apartment, and orders Eugene to knock him out. Willie barges in with a gun as Eugene flails around. He orders Eugene, under protest, to steal Lloyd’s car keys. They tell Lloyd they plan to “borrow” his car for twenty-four hours. If he contacts the police sooner, Frances will accuse him of statutory rape, and trafficking in prostitution. On the road, they find a barn to stay for the night. There, Frances does not believe Willie is a famous blues harmonica player, who will lead Eugene to the missing song, and thinks Eugene is a fool to trust him. Eugene is angered by her cynicism, but apologizes and asks her to continue on the trip. They make love but are soon interrupted by sheriff’s deputies, who detain the friends. Sheriff Tilford sends them to the next county out of his jurisdiction. Later, Willie suggests Eugene play a few songs at a local bar, then use his gun to rob customers. Feeling uncomfortable, Eugene accuses Willie of being a con man, and Willie tells him to go home to his mother. Then, Willie goes to drum up some money at a bar frequented by black patrons. After Frances fails in her attempt to pick the pocket of a customer, the friends search for Willie inside the bar. Locals taunt Eugene and Frances until Willie gets on stage with his harmonica and invites Eugene to join him. They spontaneously launch into a set and people dance. Eugene is complimented by the bar owner, but Willie laces into him, claiming Eugene still has not acquired enough experience to be great. Later, Willie has nightmares about Robert Johnson’s ghost. In the early morning, Willie catches Frances before she leaves for Los Angeles, California, to seek her fortune as a dancer. He cannot convince her to stay, but gives her some travel money. When Eugene discovers Frances is gone, Willie will not discuss it. He does admit that there is no missing song. He lied so that Eugene would help him escape from the rest home. As Willie and Eugene get closer to Fulton’s Point, they stop at a former brothel turned boarding house, where Willie asks for directions to the crossroads from the granddaughter of a former lover. They get a ride to the spot and Willie instructs Eugene to play under a dead tree. Soon, the Devil appears in a new suit. Willie says their deal is off and asks that the contract be destroyed. He claims not to have received anything that he was promised, but the Devil responds that nothing ever turns out the way it should, and sees no reason to break their agreement. Willie offers money, but the Devil wants to put Eugene in a contest with another musician named Jack Butler. Willie does not want Eugene to cut any deals, but Eugene thinks he is helping Willie, and does not perceive a threat. At a club, as Willie and Eugene watch Jack Butler play, Willie gives a Louisiana voodoo charm to Eugene to bolster his confidence and help him win. The Devil takes a seat, and Jack throws down some heavy metal guitar licks. Eugene answers by playing his own power chords. It goes back and forth. When Eugene looks like he might be in trouble, Willie joins him on stage with his harmonica. Jack stirs up the crowd with his showmanship and theatricality, but Eugene responds by laying down some choice notes. Soon, Jack runs out of steam, puts down his guitar, and walks off the stage. Eugene and Willie resume their spirited playing, and end with a rousing finale. The next day, Willie and Eugene walk by the crossroads, and Willie says he is tired of Mississippi and wants to introduce Eugene to big time musicians in Chicago. However, he warns Eugene that after Chicago, he will be on his own. He insists that Eugene take the music some place other than where he found it.