Margarethe Tiesel, born on 22 February 1959 in Vienna, Austria, studied acting at the "Mozarteum", the Salzburg University of Music and Performing Arts, from 1981 to 1983. In 1983, the year she graduated, she was appointed to the ensemble of the Dortmunder Stadttheater in Germany, to which she belonged until 1985. This was followed by engagements at the Württembergische Landesbühne Esslingen (1985-1989) and at the Städtische Bühnen Freiburg (1989-1993). She has also appeared in productions at the Düsseldorfer Schauspielhaus and the Schauspiel Frankfurt as well as at the Salzburg Festival, the Vienna Theater in der Josefstadt and the Schauspielhaus Graz.

After occasional appearances in feature films in the mid-1980s, Tiesel regularly played minor roles in film and television productions from the mid-1990s onwards. From 2000 to 2008 she had a recurring role in the Austrian crime series "Trautmann".

In 2009 Ulrich Seidl cast her for her first leading role in a feature film: In "Paradies: Liebe" ("Paradise: Love") she portrayed a 50-year-old Viennese woman who travels to Kenya as a sex tourist in the hope of perhaps also finding great love there. The film celebrated its world premiere in 2012 in the competition of the Cannes Film Festival. Margarethe Tiesel was nominated for the European Film Award. At the Austrian Film Award 2013 she received the prize for Best Actress for this role.

Also in the following years Tiesel starred regularly in cinema and television productions. Director Peter Kern cast her in two films: In "Sarah und Sarah" ("Sarah & Sarah", AT 2014) as the nurse of a demented Nazi actress and in the large ensemble of his bitter society portrait "Der letzte Sommer der Reichen" ("The Last Summer of the Rich", AT 2014). In the Wolf Haas film adaptation "Das ewige Leben" ("Life Eternal", DE/AT 2015) she was an old friend of the private detective Brenner (Josef Hader), in the horror film "Angriff der Lederhosenzombies" ("Attack of the Lederhosen Zombies", AT 2016) she had a leading role as an Tyrolian innkeeper. Ed Herzog cast Tiesel for his Bavarian crime comedies "Schweinskopf al dente" (2016) and "Grießnockerlaffäre" (2017) as the wife of a provincial police chief. She also played guest roles in series and crime thriller series and continued to appear on stage as a member of the Schauspielhaus Graz ensemble.

Margarethe Tiesel also had an important role in Fatih Akin's "Der goldene Handschuh" ("The Golden Glove"), which premiered in the competition of the Berlinale 2019. In the film she played a friend of the infamous Hamburg women murderer Fritz Honka (1935-1998).