In 1994, Mayenburg began his studies at the Hochschule der Künste in Berlin. His first play, Haarmann, was first performed at Baracke (Deutsches Theater in Berlin) in 1996. Since 1999 he is dramaturg and writer-in-residence at the Schaubühne am Lehniner Platz in Berlin.
Fireface (German: Feuergesicht), written in 1997, was his breakthrough as a dramatist. The play was performed at Munich Kammerspiele the following year. Then it was played at the Kleist Theater in Frankfurt (Oder) and at the Deutsches Schauspielhaus in Hamburg. The Hamburg performance gained the most attention. His play Perplex saw its English-language premiere in April 2014 at the Sydney Theatre Company, Australia