Bates won the Academy Award for Best Actress for her performance as Annie Wilkes in Rob Reiner's psychological thriller Misery (1990).

She received three nominations for the Academy Award for Best Supporting Actress for her performances as a tough media consultant in the Mike Nichols political satire Primary Colors (1998), a free spirited hippie in Alexander Payne's comedy-drama About Schmidt (2002), and as the mother of a bomb suspect in Clint Eastwood's biographical drama film Richard Jewell (2019).

For her performances on television she has received thirteen Primetime Emmy Award nominations winning two awards for Primetime Emmy Award for Outstanding Guest Actress in a Comedy Series for playing The Ghost of Charlie Harper in the CBS sitcom Two and a Half Men (2012), and for Primetime Emmy Award for Outstanding Supporting Actress in a Limited or Anthology Series or Movie for playing Delphine LaLaurie in the FX horror anthology series American Horror Story: Coven (2014).

On stage, Bates originated the role of Jessie Cates, a divorced woman who lives with her widowed mother, on Broadway in the Marsha Norman play 'night, Mother (1983) earning a nomination for the Tony Award for Best Actress in a Play.

Bates also originated the role of Frankie, a waitress in love, in Terrence McNally's romantic play Frankie and Johnny in the Clair de Lune (1988) where she won the Obie Award for Distinguished Performance by an Actress and was nominated for the Drama Desk Award for Outstanding Actress in a Play.