Born in Dulmen, Germany on July 22, 1974, Potente began training as an actress while in high school in Germany and continued to study her craft while attending high-school in Houston, Texas. For two years, she studied at Munich's Otto Falkenberg School of Performing Arts. It was during her schooling in Munich that she earned the Bavarian film award for "Best Newcomer" in the movie "Nach funf im Urwald".
Potente received critical praises for her work in several subsequent German films, but in "Lola rennt"(English translation is Run, Lola, Run) (1998) that put her on the international cinematic map. "Run, Lola, Run" is a film about fate and destiny and how one small moment could change the "happenings" in a person's life. In "Run, Lola, Run" Potente's character, Lola, runs through town desperately trying to collect money to save her boyfriend Mani. The film, which was written and directed by her boyfriend Tom Tykwer, received a Bambi award in 1998 and in the following year, Potente received an Audience Award for German Actress of the Year (1999).
The exposure Potente received from "Run,Lola,Run" was so heightened that she found herself being considered for many big screen Hollywood roles. She finally settled on a role that called for her to lose her accent and to refine her English speaking skills. That role came in the form of Barbara, the stewardess/drug courier in Ted Demme's cocaine-trade epic, "Blow" (2001). In 2002 co-starred with Matt Damon in "The Bourne Idenitity" (2002). In "The Bourne Identity", Potente played Marie Kreutz, a woman that Damon's character kidnaps but soon helps him as he discovers his own lost identity. She reprised the role for the popular 2004 sequel "The Bourne Supremacy," after appearing in a diverse array of international films, including the little-seen romantic comedy "Try Seventeen" (2002), a dual role in the unique German clone drama "Blueprint" (2003) and actor Adam Goldberg's directoral debut "I Love Your Work" (2003).
She has recently had a role on American Horror Story as Anne Frank, and had a recurring role on the showcase series Copper.