Rene Marie Russo was born on February 17, 1954, in Burbank, California, to Shirley Balocca, a factory worker and barmaid, and Nino Russo, a sculptor and car mechanic who left the family when Rene was just two years old. Growing up, she had to wear a full-torso brace due to scoliosis, earning her the nickname "Jolly Green Giant" from her classmates.

She attended Burroughs High School, where she was classmates with director Ron Howard, but dropped out in the tenth grade due to bullying and financial difficulties.

Rene Russo began her career as a fashion model in the 1970s, appearing on magazine covers such as Vogue and Cosmopolitan. She was spotted at a Rolling Stones concert by John Crosby, an agent from International Creative Management, and soon signed by Ford Modeling Agency.

She became one of the top models of the 1970s and early 1980s, appearing in numerous advertisements and magazine covers. She made her film debut in the 1989 comedy Major League, but it was her roles in action and thriller films throughout the 1990s that brought her international prominence.

She starred in films such as Lethal Weapon 3, In the Line of Fire, Outbreak, Get Shorty, Ransom, Lethal Weapon 4, and The Thomas Crown Affair. After headlining the family comedy Yours, Mine & Ours in 2005, Rene took a five-year break from acting.

She returned to the screen as Frigga, the mother of the titular hero, in the superhero film Thor in 2011, a role she reprised in Thor: The Dark World and Avengers: Endgame.

In 2014, she starred in the acclaimed crime thriller Nightcrawler, for which she won the Saturn Award for Best Supporting Actress and was nominated for the BAFTA Award for Best Actress in a Supporting Role. She has also appeared in The Intern, Just Getting Started, and Velvet Buzzsaw.

Rene Russo is married to screenwriter and director Dan Gilroy, and they have one daughter, Rose Gilroy, born on August 31, 1993. The couple lives in Brentwood, California.