Davis was born to William and Lucille Davis (a civil engineer and a teacher's assistant, respectively). One of the first signs of her interest and great skill in the performing arts was her budding talent in music. She learned piano, flute and drums, and she also played organ well enough even as a teenager to serve as an organist at her church in Wareham. Enrolling at New England College, Davis eventually graduated with a bachelor's degree in drama from Boston University in 1979. While an exchange student in Sandviken, Sweden, Davis became fluent in Swedish.

After graduating, Davis signed with New York's Zoli modelling agency and served as a window mannequin for Ann Taylor. With a height of six feet and a shoe size of 9(US)/40(EUR), Davis was a striking model cast from a different mold. She was working as a model when director Sydney Pollack spotted her and cast her in Tootsie (1982) as a soap opera actress. She followed this up with roles in the short-lived television series Buffalo Bill (1983–1984) and Sara (1985). Davis made a breakthrough with The Fly and Beetlejuice. She received an Oscar as Best Supporting Actress for her role in The Accidental Tourist (1988) and a Best Actress nomination for her role in Thelma and Louise (1991). Davis replaced Debra Winger for the lead in A League of Their Own, but her first vehicle Hero was a box office flop. Following this, Davis teamed up with then husband Renny Harlin for the box office disasters Cutthroat Island and The Long Kiss Goodnight.

Davis starred in the short-lived sitcom The Geena Davis Show (2000–2001). In early 2004, she guest-starred as Grace Adler's sister Janet on the NBC sitcom Will & Grace. She most recently starred in the ABC television series Commander in Chief as the first female President of the United States, who ascends to the office after the sitting president dies. This role garnered her a Golden Globe for Best Actress in a Drama Series in 2006, and she also was nominated for a SAG Award for Outstanding Female Actor in a Drama Series and an Emmy. However, almost from its premiere, the show was managed poorly by ABC[citation needed]. This led to two extended breaks and a substantial loss of viewers, resulting in the cancellation of the series during the May 2006 "sweeps" period. The series finale aired on June 14, 2006.

Davis has been married four times, including her current marriage. Her ex-husbands include Jeff Goldblum (with whom she co-starred in three films, including The Fly and Earth Girls Are Easy) from 1987 to 1990 and Renny Harlin (who directed her in Cutthroat Island as well as The Long Kiss Goodnight) from 1993 to 1998. She has been married to Iranian-American Dr. Reza Jarrahy since September 1, 2001, with whom she has three children: daughter Alizeh Keshvar (born April 10, 2002) and fraternal twins Kian William Jarrahy and Kaiis Steven Jarrahy (delivered by Caesarean section on May 9, 2004).

Davis is fronting the Women's Sports Foundation campaign Geena Takes Aim in support of Title IX — an Act of Congress focusing on equality in sports opportunities and eventually expanded to prohibit gender discrimination in United States' educational institutions.