Prefontaine is about the life of an Oregon runner in the 1960s and 1970s who held every American record for distances between 2000 and 10,000 meters. Steve Prefontaine (Jared Leto) entered the University of Oregon in 1969 as a celebrated athlete. He established a close relationship with track coach Bill Bowerman (R. Lee Ermey) who was highly enthusiastic about his discipline, guts, and desire to win.

In his first dramatic feature film, director Steve James (Hoop Dreams) uses documentary-style interviews with family and friends to draw a bead on Pre's gung-ho attitudes as America's distance prodigy. Although this runner's highest hope was to win gold at the 1972 Munich Olympics, he couldn't pull off the feat. The last part of the film shows that Pre learned from defeat how to become a team player.

One of his coaches once asked him, "You run like a prize-fighter. Are you mad at something?" For years, he was proving himself but it was only near the end of his brief life that Prefontaine reached out to help others and achieved something more fulfilling and lasting than Olympic gold.