Mark Waschke was born as second of 3 sons in Wattenscheid, Germany. His father was a surgeon and his mother a nurse. In 1980, his father was accepted as head of surgery at a hospital in Sulzbach, Saarland, and the family moved to Friedrichsthal. Waschke joined the local children´s theater and later an amateur theater group.

In 1991, Waschke moved to Berlin. After Zivildienst he began to study philosophy, which he broke off for acting. From 1995 until 1999 he studied acting at the Ernst Busch Academy of Dramatic Arts.

From 1999 until 2008, Waschke was a regular staff member of the Berlin theatre company Schaubühne under Thomas Ostermeier, who has described him as "a goodlooking, virile actor, who takes full responsibility for his play and display of emotional diversity.

Since 2005, Waschke has appeared in television series and films, notably Buddenbrooks, directed by Heinrich Breloer, 2008, Habermann (2010), The City Below, directed by Christoph Hochhäusler, 2010 Summer Window, directed by Hendrik Handloegten, 2011 and Generation War, directed by Philipp Kadelbach, 2013.

In 2006, he performed at the Deutsches Theater Berlin in Kasimir und Karoline by Ödön von Horváth (directed by Andreas Dresen) and in 2009 at the Maxim Gorki Theater Berlin in Leonce and Lena by Georg Büchner , directed by Jan Bosse.

In 2009, Waschke won the Prize for Best Actor in a leading Role at the Roma Fiction Fest and the Bavarian Film Awards for Best Actor in Habermann, in 2012 he was awarded the Franz-Hofer-Prize and in 2013 he won the German Actors Award.

Since the 2013/14 season, he has rejoined the Schaubühne. He has said, that acting on stage is a mental and physical need, not only because it does not get interrupted as in filming but also "for a different kind of responsibility, for oneself, the role, the play, the great ritual, which at best doesnt only do something for the audience [...]. In a rare moment it becomes utopia."