In 1969, she played the lead role in Peter Fleischmann's film Jagdszenen aus Niederbayern.

Her next film, The Lost Honour of Katharina Blum, directed by Volker Schlöndorff and Margarethe von Trotta, made her a star in 1975.

In 1979, she won international fame as the mother of Oskar Matzerath in Schlöndorff's Oscar-winning film The Tin Drum, an adaption of the famous book of the same name by Günter Grass.

More recently, Winkler appeared in Dark (2017), the first German-language Netflix original series, and as Miss Tanner in Luca Guadagnino's Suspiria (2018).

Her daughter Nele, who has Down's syndrome, is also an actress; she had a role in Dora or The Sexual Neuroses of Our Parents and is a member of the ensemble at RambaZamba theatre in Berlin.