Recent Georgetown University graduates Alec, Leslie, Kevin, Jules, and Kirby are waiting to hear about the conditions of their friends: Wendy, a sweet-natured young woman devoted to helping others, and Billy, a former fraternity boy and now reluctant husband and father, after a minor car accident caused by Billy's drinking. At the hospital, Kirby spots a medical student named Dale, with whom he has been infatuated since college.
The group gathers at their favorite college hangout, St. Elmo's Bar. Billy, trapped in an unstable marriage, has been fired from the job that Alec helped him secure. At their apartment, Alec pressures Leslie to marry him, but she thinks they are unprepared to make such a commitment. Kirby is telling Kevin of his love for Dale when Billy shows up, asking to spend the night as he cannot cope with his wife. Jules accuses Kevin of being gay and loving Alec. When Kevin visits Alec and Leslie for dinner, Alec, during a private moment with Kevin, confesses he recently had sex with a lingerie saleswoman.
Billy and Wendy get drunk together, and Wendy reveals that she's a virgin. They kiss, and Billy, tugging at her clothing, makes fun of her girdle. Wendy insists they just remain friends because she thinks that he's trying to take advantage of her. At St. Elmo's, Jules reveals to Leslie she is having an affair with her married boss. Billy sees his wife with another man in the crowd and attacks him. Billy is thrown out of the bar but reconciles with his wife. The women confront Jules about her affair and reckless spending, but she insists that everything is under control.
Kirby takes a job working for Mr. Kim, a wealthy Korean businessman, and invites Dale to a party that he's holding at Mr. Kim's house (which he is using without Mr. Kim's permission). Wendy arrives with Howie, an ungainly Jewish boy whom her parents want her to marry. Alec announces that he and Leslie are engaged, upsetting her. She confronts him about her suspicions of his infidelity, and the two break up. Alec accuses Kevin of telling Leslie about the tryst with the lingerie woman. Jules gives Billy a ride home, and Billy makes a pass at her. Furious, Jules orders him out of her car, and Billy's wife witnesses the confrontation.
When Dale skips the party, Kirby drives to the ski lodge where she is staying and meets her tall, handsome boyfriend. Kirby's borrowed car gets stuck, and Dale and her boyfriend invite him in. The next morning, as Kirby prepares to leave the lodge, Dale tells him that she's flattered by his interest in her. He kisses her, and then poses for a photo with her (taken by her boyfriend) before leaving. Dale watches Kirby as he drives off.
Leslie goes to Kevin's apartment to spend the night after the breakup and discovers photographs of her. Kevin confesses his love for her, and the two sleep together. Alec goes to the apartment to apologize to Kevin and finds Leslie there, and then Alec and Leslie argue.
Wendy tells her father that she wants to be independent and move into her own place. Jules has been fired from her job, fallen behind on her credit card payments, and her possessions have been seized. Jules locks herself in her apartment and opens the windows, intending to freeze to death. Her friends attempt to coax her out, but she is unresponsive. Kirby fetches Billy, who landed a job at a gas station courtesy of Kevin, to calm Jules down. Billy convinces Jules to let him in, and the two share a very tender talk about the challenges of life, overheard by the rest of the gang.
Wendy moves into her own place, where Billy visits and informs her that he is getting a divorce and moving to New York City, and the two have sex. At the bus station, the group gathers once more to say goodbye to Billy. Billy urges Alec to make up with Leslie, but she declares that she does not want to date anyone for a while. Alec and Kevin make up, and the group makes plans to meet for brunch. However, they decide not to go to St. Elmo's and instead choose Houlihan's because there are "not so many kids" there.
Emilio Estevez as Kirby "Kirbo" Keager, a law student and waiter at St. Elmo's Bar.
Rob Lowe as Billy Hicks, a saxophonist "frat boy" and reluctant husband and father.
Andrew McCarthy as Kevin Dolenz, a writer for The Washington Post with a sullen streak, and Kirby's roommate.
Demi Moore as Julianna "Jules" Van Patten, an international banker and the "party girl" of the group.
Judd Nelson as Alec Newbury, a yuppie pursuing a career in politics.
Ally Sheedy as Leslie Hunter, a budding architect who is reluctant to marry Alec.
Mare Winningham as Wendy Beamish, a social worker from a wealthy family and devoted to helping others.
Martin Balsam as Mr. Beamish, Wendy's father.
Andie MacDowell as Dale Biberman, a hospital intern and the object of Kirby's affection.
Joyce Van Patten as Mrs. Beamish, Wendy's mother.
Jenny Wright as Felicia Hicks, Billy’s wife.
Blake Clark as Wally
Jon Cutler as Howie Krantz
Matthew Laurance as Ron Dellasandro
Gina Hecht as Judith
Anna Maria Horsford as Naomi