In 1987, she began modeling at the age of 12 when Herb Ritts photographed her for the cover of the Italian magazine Lei. Richard Avedon featured her in Revlon's "Most Unforgettable Women in the World" advertisements.In 1988, Jovovich had her first acting role in the television film The Night Train to Kathmandu, and that year also appeared in her first feature film, Two Moon Junction.
In 2002, Jovovich starred in the science fiction horror film Resident Evil, adapted from the video game series of the same name. It was disliked by critics, but was commercially successful.She reprised her role in four sequels, all in the apocalyptic fiction action horror genre, made between 2004 and 2012.