Lange received critical praise for her performance as Cora in Bob Rafelson's remake of the classic The Postman Always Rings Twice and earned her first Academy Award nomination for her next film, Frances, based on the life of Frances Farmer. That film segued almost immediately into work on Tootsie, for which she won the Best Supporting Actress Oscar in 1983. This marked the first time in 25 years that an actor had been nominated for two Oscars in the same year. She went on to both produce and star in Country, after which she portrayed country western legend, Patsy Cline, in Sweet Dreams opposite Ed Harris. She received Best Actress nominations for both of performances. Lange next starred in Crimes of the Heart followed by Far North and Everybody's All-American. She went on to star in Men Don't Leave and Music Box, which earned her a fifth Academy Award nomination. Soon after, she starred in Martin Scorsese's remake of Cape Fear and Night and the City. Other films include Rob Roy and Losing Isaiah.

Lange made her Broadway debut in 1992 as Blanche Dubois in Gregory Mosher's revival of Tennessee Williams' A Streetcar Named Desire. She then reprised her role as Blanche in the London run of the production in 1996. Lange appeared again as Blanche Dubois in the CBS Playhouse '90s presentation of A Streetcar Named Desire with John Goodman.

1995 was an exceptional year in which she won the Best Actress honor at both the Academy Awards and the Golden Globes for her performance in Blue Sky opposite Tommy Lee Jones.

In 1997-98 Lange again received critical praise for her performances in three films: A Thousand Acres, Hush and Cousin Bette. Most recently, Lange starred in Titus. She followed this with a hugely successful turn on the London stage in Long Day's Journey Into Night.