In the 1999 film Introducing Dorothy Dandridge, Berry portrayed the first black woman to be nominated for a Best Actress Academy Award. In this HBO biopic, Berry’s performance was recognized with several awards including an Emmy and a Golden Globe. (She was also one of the producers of the project.)

Berry portrayed the mutant Storm in the movie adaptation of the popular comic book series X-Men (2000) and its successful sequels X2: X-Men United (2003) and X-Men: The Last Stand (2006). In late 2001, Berry appeared as Leticia Musgrove, the wife of an executed murderer, in the film Monster’s Ball. Her performance was awarded the National Board of Review and the Screen Actors Guild prizes. The role earned her an Academy Award for Best Actress: she made history by becoming the first African American woman to earn a Best Actress Academy Award.

As Bond Girl Jinx in the (2002) blockbuster Die Another Day she famously re-created the scene from Dr. No, bursting from the surf to be greeted by James Bond, as Ursula Andress had 40 years earlier. In late 2003, Berry starred in the psychological thriller Gothika opposite Robert Downey Jr. Her next lead role was in the film Catwoman, for which she was awarded a "worst actress" Razzie award in 2005, which she accepted in person with a sense of humor and recognition that "to be at the top, you must experience the rock bottom".