"Crash" Davis (Kevin Costner), a veteran of 12 years in minor league baseball, is sent down to the single-A (advanced) Durham Bulls for a specific purpose: to educate hotshot rookie pitcher Ebby LaLoosh (Tim Robbins, playing a character loosely based on Steve Dalkowski) about becoming a major-league talent, and to control Ebby's haphazard pitching. Crash immediately begins calling Ebby by the degrading nickname of "Meat", and they get off to a rocky start.
Thrown into the mix is Annie (Susan Sarandon), a lifelong spiritual seeker who has latched onto the "Church of Baseball" and has, every year, chosen one player on the Bulls to be her lover and student. Annie flirts with Crash and Ebby, but Crash walks out, saying he's too much a veteran to "try out" for anything. Before he leaves, Crash further sparks Annie's interest with a memorable speech listing the things he "believes in", ending with "I believe in long, slow, soft, deep wet kisses that last three days... Good night".
Despite some animosity between them, Annie and Crash work, in their own ways, to shape Ebby into a big-league pitcher. Annie plays mild bondage games, reads poetry to him, and gets him to think in different ways (and gives him the nickname "Nuke"). Crash forces Nuke to learn "not to think" by letting the catcher make the pitching calls (memorably at two points telling the batters what pitch is coming after Nuke rejects his calls), and lectures him about the pressure of facing major league hitters who can hit his "heat" (fastballs). Crash also talks about the pleasure of life in "The Show" (Major League Baseball), which he briefly lived for "the 21 greatest days of my life" and to which he has tried for years to return.
Meanwhile, as Nuke matures, the relationship between Annie and Crash grows, until it becomes obvious that the two of them are a more appropriate match, except for the fact that Annie and Nuke are currently a couple.
After a rough start, Nuke becomes a dominant pitcher by mid-season. By the end of the movie, Nuke is called up to the majors and the Bulls, now having no use for his mentor, release Crash. This incites jealous anger in Crash, who is frustrated by Nuke's failure to recognize all the talent he was blessed with. Nuke leaves for the big leagues, ending his relationship with Annie, and Crash overcomes his jealousy to leave Nuke with some final words of advice.
Crash joins another team, the Asheville Tourists, and breaks the minor league record for career home runs. We see Nuke one last time, being interviewed by the press as a major leaguer, reciting the clichéd answers that Crash had taught him earlier. Crash then retires as a player and returns to Durham, where Annie tells him she's ready to give up her annual affairs with "boys". Crash tells her that he is thinking about becoming a manager for a minor league team in Visalia. Both characters end one phase of their lives and begin another, Annie and Crash dancing in her candle-lit living room.