Nele Mueller-Stöfen was born on 7 May 1967 in Hamburg. After graduating from high school, she studied acting at the Hochschule für Musik und darstellende Kunst in Graz and received her first stage engagements in Münster and Düsseldorf after completing her training. In 1993 Mueller-Stöfen was awarded the North Rhine-Westphalian Young Performers' Prize; her other theatre stations include Kampnagel in Hamburg and the Renaissance Theatre in Berlin.

From 1992 Nele Mueller-Stöfen also appeared in television and cinema productions. First roles in Rainer Kaufmann's "Einer meiner ältesten Freunde" (1994), Sönke Wortmann's comedy "Das Superweib" ("The Superwife", 1996) and the satire "Peanuts - Die Bank zahlt alles" (1996) established her as a versatile and sought-after actress. TV leading roles in Roland Suso Richter's "Buddies" (1996) and Christian Petzold's "Die Beischlafdiebin" ("The Sex Thief", 1998) were followed by roles in "Gierig" (1999) and "Frau2 sucht Happy End" ("Female2 Seeks Happy End", 2000). A regular collaboration also developed with director Lars Kraume, who directed Mueller-Stöfen in "Dunckel" (1998), "Viktor Vogel - Commercial Man" (2001), "Guten Morgen, Herr Grothe" ("Good Morning Mr. Grothe", 2007) and "Familienfest" (2015).

In addition to her successful acting career, Nele Mueller-Stöfen has also made a name for herself as a scriptwriter. Together with her husband, director Edward Berger, she wrote the script for "Jack" (2014), a much-discussed drama about two underage brothers who roam the big city in search of their mother. "Jack" celebrated its premiere in the Berlinale competition, and in 2015 Berger and Mueller-Stöfen were nominated for the German Film Prize in the category Best Screenplay.

As an actress, Mueller-Stöfen was seen in a leading role in the TV tragicomedy "Besser spät als nie" (2015), about a family that almost breaks up because of their spatial separation. She has also played guest roles in several series, including "Der Bergdoktor" (2017) and "Die Spezialisten - Im Namen der Opfer" (2017).

Together with Edward Berger, she wrote the script for "All My Loving" (2019), about three unequal siblings coming to a turning point in their lives. The film, in which Mueller-Stöfen also played a leading role, celebrated its premiere in the Berlinale competition, as "Jack" had before.