Jovovich has been described by Paul W.S. Anderson, director of her film Resident Evil, as a "rare combination of a good actress who could kick ass and look beautiful doing it." Music channel VH1 has referred to her as the "reigning queen of kick-butt".

Jovovich was born in Kiev, Ukraine (then part of the Soviet Union) to Bogdan Jovovic, a Serbian medical doctor, and Galina Loginova, a Russian actress. Her paternal family is Montenegrin, their estate being at Metohija in Zlopek near Peć. Many Croats and Serbs claim Jovovich is a Croatian or Serbian, but this assertion is in fact erroneous. Her paternal great-grandfather, Bogic Camic Jovovic, was flag-bearer of the Vasojevici clan and officer of the guard of the King Nicholas I of Montenegro; his wife's name was also Milica. Her paternal grandfather, Bogdan Jovovic, was a commander in the Pristina military area, and later investigated finances in military areas of Skopje and Sarajevo, where he uncovered massive gold embezzlement. He was punished for refusing to convict his friend for the crime. Later, the communist government imprisoned him on Goli Otok. When he feared that he could be arrested again, he escaped to Albania and later moved to Kyiv. Another version of the story claims that he was the one to have taken the gold. Milla's father, Bogic Jovovic, later joined her grandfather in Kyiv, where he and his sister graduated in medicine.

In 1981, The family moved to London, and subsequently lived in Sacramento, California. Seven months later, they settled in Los Angeles, California.

Milla Jovovich, 11, on the cover of Italian magazine LeiAt the age of eleven, Jovovich was spotted by the photographer Richard Avedon, who featured her in Revlon's "Most Unforgettable Women in the World" advertisements. In October 1987, she was featured on the cover of the Italian fashion magazine Lei, which was the first of her many cover shoots. She continued to model and in 1988, appeared in her first film role, the romance thriller Two Moon Junction.

In 1991, Jovovich had a starring role in the romance adventure sequel Return to the Blue Lagoon, opposite Brian Krause, which led to comparisons between her and child model-turned-actress, Brooke Shields (who had starred in the original Blue Lagoon). For her role, she was nominated for both 'Best Young Actress Starring in a Motion Picture' in the 1991 Young Artist Awards, and 'Worst New Star' in the 1991 Golden Raspberry Awards. Most of Jovovich's film appearances during the early 1990s were in supporting or cameo roles.

In 1994, Jovovich, billed under her first name, released her critically acclaimed first musical album, The Divine Comedy. Featuring unique-sounding songs that fused pop with traditional Russian folk music influences, the album led to comparisons with musicians Tori Amos and Kate Bush. After leading a band called Plastic Has Memory, Jovovich returned to her acting career, receiving top billing and entering the world of action heroes, with her performances in The Fifth Element (1997) and in two popular films based upon the survival horror series, Resident Evil.

Jovovich's vocals appeared on the 2004 album Legion of Boom by The Crystal Method. She also recorded the single Rocket Collecting, which appeared on the soundtrack for the film Underworld.

Jovovich and fellow model Carmen Hawk have launched a line of clothing called Jovovich-Hawk; the two opened a showroom in New York City's Greenwich Village on September 13, 2005. Jovovich is also an "international spokesmodel" for L'Oreal cosmetics and was the highest paid supermodel in 2004. In 2006 Jovovich was picked up by Spanish clothing line Mango as their new spokesmodel. Mango told Vogue.com that Jovovich is "the image of the woman that [we] wish to dress: a very modern woman, with personality and self-confidence". She has said that she enjoys having both a modelling and an acting career, and that she is "very grateful for [her] looks", which allow her to "make really great film choices".

Jovovich's latest film, the science fiction/action thriller Ultraviolet, was released on March 3, 2006. It was not screened for critics, but when reviewed, it was critically panned. It has grossed $17 million at the domestic box office. She will appear in the third film in the Resident Evil series.

Jovovich is also planning to publish her private diaries as an autobiography. Jovovich says, "I've been keeping a diary ever since I was a little girl. I've written about all the places I've been to and all the mad things that I've done, so it would be good to get it all into a book - like an autobiography, but with more of a diary feel to it. I'm not sure how interested anyone would be in publishing it, or reading it, for that matter."

Jovovich married actor Shawn Andrews in October of 1992, while filming Dazed and Confused together; the marriage was annulled a month later. She married The Fifth Element director Luc Besson in 1997, but the two divorced in 1999. Jovovich also dated Red Hot Chili Peppers guitarist John Frusciante for several months in 2000 and was linked to actor Stephen Dorff. She also had a relationship with Jamiroquai ex-bassist Stuart Zender, during which time they both lived in London. Most recently she has appeared in public with Japanese soccer star Nakata Hidetoshi, but is purported to be engaged to writer/director Paul W. S. Anderson.