Aurora Greenway (Shirley MacLaine) and her daughter Emma (Debra Winger) are both searching for deep romantic love. The film opens with Emma's early childhood, Aurora reveals how difficult and caring she can be by nearly climbing into Emma's crib in order to make sure her daughter is breathingonly to be reassured when Emma starts crying (after being woken up). After the death of Aurora's husband and Emma's father, Rudyard, Aurora and Emma develop an extremely close love-hate mother/daughter relationship as Emma grows up.
Skipping forward several years, Emma gets married immediately upon graduating from high school in the Houston area, to Flap Horton (Jeff Daniels), of whom Aurora so disapproves that she refuses to attend the wedding. Emma's best friend Patsy Clark (Lisa Hart Caroll) continues on to college, eventually becoming successful and rich in New York City.
Over the next few years, Emma has two children with Flap, a college professor who relocates the family to a university in Des Moines, Iowa, separating the family hundreds of miles from Emma's meddlesome mother. Emma later telephones to ask her mother for money when she is pregnant with her third child. Aurora, not knowing by the telephone call that Emma is already several months into her pregnancy, wants Emma to get an abortion. Emma's once-passionate marriage to Flap becomes strained, thanks mostly to his philandering. Emma eventually has a secret romantic affair of her own with a married small-town older banker, Sam Burns (John Lithgow).
Meanwhile back in Houston, Aurora remains celibate but cultivates the attention of several gentlemen in the area, some rather bizarre. However, she is attracted to her next-door neighbor of 15 years, the womanizing, alcoholic retired astronaut Garrett Breedlove (Jack Nicholson). Aurora and Garrett eventually go on a lunch date, make love, and develop a tenuous relationship.
Emma returns to her mother's home in Houston after discovering her husband is having an affair with a young grad student named Janice (Kate Charleston). Emma's appearance along with her three young children makes Garrett uncomfortable, as he has been single for a long time. Flap telephones and she reluctantly returns home to Iowa, trying to reconcile with him. Unwilling to become a one-woman man, Garrett breaks up with Aurora, making her feel "humiliated."
Emma ends her relationship with Sam as soon as Flap accepts a new teaching position in Kearney, Nebraska. Although she does not want to, Emma agrees to relocate to further Flap's career. She soon discovers that Janice is attending the same college where Flap now works, realizing that Flap followed her to Nebraska. Emma angrily confronts Janice before taking daughter Melanie to the doctor's office so both can get flu shots. While administering the injection, Emma's doctor notices two large lumps under Emma's armpit. Although Emma is only in her 30s, the doctor orders a biopsy and discovers she has cancer.
To cheer her up, Patsy invites Emma to New York City for her first vacation without her children. However, after arriving, Emma feels out-of-place among Patsy's friends and returns home early to begin chemotherapy treatment for her illness. Her doctor soon breaks the news that the drugs she was taking did not have the desired effect, and that Emma will not survive her illness. Flap and Aurora remain by her bedside in the hospital for weeks. Although devastated and exhausted, Aurora is still very supportive and loving towards Emma. Garrett flies to Lincoln, Nebraska, where he surprises Aurora, who confesses her love for him. He issues his stock reply: "I love you, too, kid."
In a discussion in the hospital cafeteria, Aurora tells Flap bluntly that he does not have the energy managing a job, chasing women, and raising children. Patsy, who has no children of her own, wants to adopt Melanie, but Flap and Emma do not want their kids to be separated. Emma also doesn't want Janice to raise her children, so Flap, feeling like a failure as both a father and a husband, agrees that having them live with Aurora is best.
As Emma's time begins to run short, eldest child Tommy shows open resentment toward his mother due to circumstances such as social class, fights between his parents, and Tommy's perception of feeling unloved. Emma reassures her two sons, and, after an altercation with Aurora (she slaps him in the hospital parking lot for criticizing his mother), Tommy weeps in his grandmother's arms. Emma dies later that night.
Following the funeral, Emma's friends and family gather in Aurora's backyard for a memorial service. Garrett shows affection toward each of Emma's children and helps Tommy cope during the wake. The film closes on Aurora, sitting next to Melanie.