She was born in Topeka, Kansas, the daughter of Arnett Grant Bening (born 1926) and Shirley Bening (born 1930). Her sister and two brothers are Jane Bening (born 1953), Bradley Bening (born 1955) and Byron Bening (born 1957). Her father worked for an insurance company. The family moved to Wichita, Kansas, in 1959, where she spent her early childhood.

In 1965, Annette's father took a job with a company in San Diego, California, and they moved there. She began acting in junior high school, playing the lead in The Sound of Music. She studied drama at Patrick Henry High School and graduated in three years.

She then spent a year working as a cook on a charter boat taking fishing parties out on the Pacific Ocean, and scuba diving for recreation. She attended San Diego Mesa College, then completed an academic degree in theatre arts at San Francisco State University. Bening joined the acting company at the American Conservatory Theater in San Francisco while studying acting as part of the Advanced Theatre Training Program. During this time she established herself as a formidable acting talent in roles like Shakespeare's Lady Macbeth.

In 1985, she and her first husband, Steven White, moved to Denver, Colorado, to work at the Colorado Shakespeare Festival in Boulder. They separated the following year. Bening moved to New York City, where she debuted on Broadway in the role of 'Holly Dancer' in Coastal Disturbances by Tina Howe (1987).

Bening was nominated for a Tony Award for her performance in Coastal Disturbances, and won a Clarence Derwent Award for Outstanding Debut Performance. However, she endured a five-year struggle before breaking into motion pictures.

Her debut was the made-for-TV movie Manhunt for Claude Dallas (1986). Her first major role in a theatrical feature was in The Great Outdoors (1988) playing 'Kate Craig' opposite Dan Aykroyd, with co-stars John Candy and Stephanie Faracy. Her next role was as the Marquise de Merteuil in Valmont (1989) opposite Colin Firth. Bening's next major feature, Stephen Frears's The Grifters (1990) starring Anjelica Huston and John Cusack, met with critical acclaim. She received an Academy Award nomination for Best Supporting Actress for The Grifters.

She and Warren Beatty met on the set of Bugsy(1991), in which she played Virginia Hill, and the two began a secret romance.

She has had two husbands, choreographer J. Steven White (married 1984 - divorced 1991) and actor Warren Beatty (married 1992 - present). She and Beatty have four children, Kathlyn Elizabeth Beatty (born 1992), Benjamin McLaine Beatty (born 1994), Isabel Ira Ashley Beatty (born 1997) and Ella Corinne Beatty (born 2000). Bening is the sister-in-law of Shirley MacLaine.

Bening was paid $3,000,000 to play the role of Elise Kraft/Sharon Bridger in The Siege(1998) co-starring Denzel Washington and Bruce Willis.

She received Academy Award nominations for Best Actress in a Leading Role for American Beauty and for Being Julia (2004). She would lose both times, coincidentally, to Hilary Swank. Bening won a Golden Globe for Best Actress in a Comedy for Being Julia, in which she played a 1930s stage actress in mid-career and mid-life crises.

She has also done voice work for animation, such as that of Abigail Adams in the TV series Liberty's Kids: Est. 1776 (2002).

Annette Bening lives with her husband and children in Los Angeles, California.