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 (1994-96),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" (1995).

Potente received critical praises for her work in several subsequent German films, but it was her hot pink hair and her steel-toe boots pounding the pavement in "Lola rennt" (1998) that really put her on the international cinematic map. "Lola rennt" (translated to 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 polish 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). For Potente, the role allowed for a more poised and stylized performance. In 2002, Potente began running again, but this time 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), where she met rumored paramouer Elijah Wood; a dual role in the unique German clone drama "Blueprint" (2003) and actor Adam Goldberg's directoral debut "I Love Your Work" (2003), playing a popular actress in a story marriage to fame-unfriendly Giovanni Ribisi.