While she had been appearing in films as early as Rollercoaster in 1977, Hunt was never groomed as a star player, and it is possible that her resemblance to another child actress, Jodie Foster, held her back from more important roles.

After taking on her first adult role in the 1982 sitcom It Takes Two, Hunt's film assignments improved, with sizable roles in Girls Just Want to Have Fun (1985), Peggy Sue Got Married (1986), Project X (1987), Next of Kin (1989), and The Waterdance (1991). She also gained a small measure of cult status by appearing in a brace of science fiction films, including Trancers II (1991) and Trancers III (1992). That same year, Hunt landed her longest-lasting acting assignment to date, as the co-star of the Paul Reiser-created comedy series Mad About You. During the show's seven-year run, she won both Emmy and Golden Globe awards for her portrayal of Jamie Buchman. In 1996, Hunt had her most successful film role to date in the blockbuster Twister. The following year, she topped that when she received a Best Actress Oscar for playing a caring waitress and single mother who befriends acerbic, obsessive-compulsive author Melvin Udall (Jack Nicholson, who also won an Oscar for his performance) in As Good As It Gets. After Mad About You ended in 1999, Hunt appeared in films by several veteran directors, including Robert Zemeckis (Cast Away [2000]), Robert Altman (Dr. T and The Women [2000]), and Woody Allen (The Curse of the Jade Scorpion [2001]). She starred in Life x 3 on Broadway in 2003.