Prefontaine tells the story from the point of view of Bill Dellinger, played by Ed O'Neill, the assistant coach who was with him day-to-day, and Nancy Alleman, the runner's girlfriend at the time of his death.

Steve Prefontaine, a Coos Bay, Oregon student, is too small to play most sports but becomes a talented distance runner.

Prefontaine gains fame as an aggressive runner who likes to be out front from the start, rather than biding his time until a strong finish.

The strict amateurism rules of American non-collegiate sports force Prefontaine to turn down a lucrative offer to become a professional runner, instead working as a bartender while living in a trailer home.

For the role of Steve Prefontaine, Jared Leto immersed himself in the runner's life, meeting with members of the family and friends.