Angelica Domröse was born in Berlin-Weißensee on April 4th 1941. Already as a student, she was interested in acting, and although she initially failed the admission test at the Hochschule für Film und Fernsehen in Potsdam, she was eventually discovered by director Slatan Dudow, who cast her as the female lead for "Verwirrung der Liebe" ("Love's Confusion"). Consequently, she was admitted to the acting class at the Hochschule für Film und Fernsehen in January 1959.

Following her graduation in April 1961, she joined the Berliner Ensemble. She played the role of Betty in Erich Engels' staging of Brecht's "Die Dreigroschenoper", and in the same year, she also appeared as Babettte in "Die Tage der Commune". In 1966, Domröse was named Actress of the Year and joined the Berliner Volksbühne. There she was hailed for her performances in plays like "Cäsar und Cleopatra" (1967), "Die schöne Helena" (1972), "Die Wildente" (1973) and her work in Brecht revues, which also toured internationally.

Along with her work in the theatre, Domröse regularly appeared in DEFA feature films. She played the nurse Li in "Julia lebt" (1963) and the Jewess Ruth Bodenstein in "Chronik eines Mordes" ("The Story of a Murder", 1965). Her work in television at that time included "Wege übers Land" (1968), the series "Krupp und Krause" (1969), and most notably the titular role in the Fontane adaptation "Effi Briest" (1971). During her career, she was named East Germany's TV Artist of the Year in 1971, 1973 and 1975.

In 1972, she probably played her most famous role in Heiner Carow's "Die Legende von Paul und Paula" ("The Legend of Paul and Paula"). The film was a tremendous success, but in 1980, it was taken out of distribution after Domröse and her screen partner Winfried Glatzeder left the GDR. Already in 1979, she was guest starring in West Germany, and played the role of Helena in Boy Gobert's staging of "Faust II" at the Thalia Theater in Hamburg. In 1980, she was cast by Peter Zadek for his Fallada adaptation "Jeder stirbt für sich allein" in West-Berlin. Together with frequent screen and stage partner Hilmar Thate, whom she had married in 1976, she later joined the ensemble of the Schillertheater.

After her move to the Federal Republic, she only sporadically appeared in cinema releases, and predominately worked in television. She starred in Frank Beyer's drama "Die zweite Haut" and Egon Günther's "Hanna von acht bis acht", and had memorable roles in Helmut Dietl's acclaimed satire "Kir Royal" and the comedy series "Tagesshow". She also got excellent reviews for her performance alongside Hilmar Thate in the psychological TV drama "Hurenglück" (1990) by Detlef Rönfeldt.

In 1991, she re-teamed once more with director Heiner Carow for "Die Verfehlung" ("The Mistake"), a love story set between East and West which included allusions to "Die Legende von Paul und Paula". She continued to work in TV and also proved herself as a director of theatre plays and as a lecturer at the Academy of the Arts and the renowned Ernst Busch acting school in Berlin. In 2003, she appeared in Branwen Okpako's drama "Tal der Ahnungslosen" ("Valley of the Innocent"), and the same year, she published her biography under the title "Ich fang mich selbst ein".

In 2012 Domröse played alongside Otto Sander the main character in Bernd Böhlich's "Bis zum Horizont, dann links!".

Angelica Domröse alternately lives in Berlin-Charlottenburg and at Siethener Lake; Brandenburg.