For nearly fifteen years, Stowe appeared mostly in minor or supporting roles in movies and on TV. A few of her performances from this period became, however, well-known to the public, as was the case for Stakeout (1987), where she played opposite to Richard Dreyfuss, and Revenge, (1990), which co-starred Kevin Costner. In 1992 Stowe finally performed a leading role in a high-profile film, The Last of the Mohicans, which also starred Daniel Day-Lewis.

Thereafter, several major film roles followed. The next year, director Robert Altman cast Stowe in Short Cuts, in which she gave one of her most acclaimed screen performances as the wife of a compulsive lying and adulterous police officer played by Tim Robbins. The following year, Madeleine was a blind musician in the thriller Blink, co-starring Aidan Quinn (14 years earlier, she had a guest role as a blind painter in Little House on the Prairie). The year after that, she was a sympathetic psychiatrist in the science-fiction movie