Orso made her film debut in The Bible: In the Beginning, a 1966 religious epic film directed by American film director John Huston. Over the course of her career, Orso appeared in numerous American and Italian films directed by Alberto Bevilacqua, Marco Bellocchio, Jose Dajane, Riccardo Donna, Diego Febbraro, Luciano Odorisio, Pasquale Squitieri, Massimo Troisi, and Wim Wenders.
Orso appeared in the 2003 HBO television series, Angels in America, opposite Al Pacino and Meryl Streep. She was also cast in the 2004 film, The Life Aquatic with Steve Zissou, directed by Wes Anderson. At the time of her death in 2012, Orso was filming The Girl from Nagasaki, a film adaptation of Madame Butterfly, directed by Michel Comte.
Anna Orso died in a Rome hospital of an illness on August 14, 2012, at the age of 74. She was survived by her son, Umberto. Her remains were cremated, and a memorial service was scheduled for the library of cinema in Trastevere in September 2012.
- "E' morta l'attrice Anna Orso, Aveva recitato con Al Pacino". la Repubblica. 2012-08-14. Retrieved 2012-09-11.