Natja Brunckhorst was born on September 26, 1966, in Berlin (West). She was discovered at the age of 13 in a schoolyard and cast in the lead role of the film "Christiane F. – Wir Kinder vom Bahnhof Zoo" ("Christiane F. – We Children from Bahnhof Zoo"). The film premiered in 1981 and her compelling portrayal of a teenage drug addict captivated both critics and audiences alike. The following year, she appeared in a small role in Rainer Werner Fassbinder's film "Querelle". However, the sudden media attention overwhelmed the teenager, prompting her to move to Great Britain for several years followed by a year in Paris. 

In 1987, she returned to Germany and enrolled at the Bochum Drama School, graduating in 1991. During this time, she starred as a feminist bookshop owner in Dominik Graf's TV film "Tiger, Löwe, Panther" (1989) and played another lead role in Ralf Huettner's horror film "Babylon - Im Bett mit dem Teufel" (1992). 

From 1993 to 1994, Brunckhorst took a break from acting due to a battle with cancer. In subsequent years, she appeared in various television productions, such as alongside Inga Busch in the urban fairy tale "Eine fast perfekte Liebe" (1996) and in "Das verletzte Lächeln" (1996) as a popular photo model whose life is disrupted by an accident. On the big screen, she had supporting roles in the comedy "Dumm gelaufen" ("Gone Wrong", 1997) and Tom Tykwer's film "Der Krieger und die Kaiserin" ("The Princess and the Warrior", 2000). 

In 1997, Natja Brunckhorst began working as a screenwriter, starting with the TV series "Einsatz Hamburg Süd". Her screenplay "Wie Feuer und Flamme" ("Never Mind the Wall", 2001, directed by Connie Walther), an autobiographically inspired coming-of-age story, won her the German Film Award. That same year, Brunckhorst directed her first short film "La Mer", a love story. In 2003, she was one of the founding members of the German Film Academy.

Following this, Brunckhorst appeared sporadically as an actress. In Jessica Krummenacher's film "Totem", premiered at the Venice Film Festival in 2011, she played the lead role of a woman whose family is paralyzed by silence. As a writer, she penned episodes for the "Tatort" series ("Oben und unten" in 2009, and "Dinge, die noch zu tun sind" in 2012) and the "Polizeiruf 110" episode "Und vergib uns unsere Schuld" (2016).

In 2017, Brunckhorst's youth film "Amelie rennt" ("Mountain Miracle – An Unexpected Friendship"), which she wrote, premiered in cinemas. It tells the story of an asthmatic girl who embarks on an adventurous mountain tour with a farm boy. At the 2017 Golden Sparrow Festival, Brunckhorst and director Tobias Wiemann won the award for Best German-Language Feature Film for Children.

Natja Brunckhorst made her feature film directorial debut with the relationship drama "Alles in bester Ordnung" ("Mostly Minimalistic", 2021), earning her the Best Director Award at the Festival of German Films in Ludwigshafen. She presented her second feature film as writer and director, the post-reunification tragicomedy "Zwei zu Eins" ("Two to One", 2024), at the Munich Film Festival in 2024.