Born in New York City, Bacall was the only child of Natalie Weinstein-Bacal, a secretary who later legally changed her surname to Bacall, and William Perske, who worked in sales. Her parents were Jewish immigrants, their families having come from Poland, Romania and Germany. She is first cousin to Shimon Peres, current President and former Prime Minister of Israel. Her parents divorced when she was five, and she took her mother's last name, Bacall. Bacall no longer saw her father and formed a close bond with her mother, whom she took with her to California when she became a movie star.

Bacall took lessons at the American Academy of Dramatic Arts. During this time, she became a theatre usher and worked as a fashion model. As Betty Bacall, she made her acting debut, at age 17, on Broadway in 1942, as a walk-on in Johnny 2 X 4. According to her autobiography, she met her idol Bette Davis at Davis' hotel. Years later, Davis visited Bacall backstage to congratulate her on her performance in Applause, a musical based on Davis' turn in All About Eve.

Bacall became a part-time fashion model. Howard Hawks's wife Nancy spotted her on the March 1943 cover of Harper's Bazaar and urged Hawks to have her take a screen test for To Have and Have Not. Hawks invited her to Hollywood for the audition. He signed her up to a seven-year personal contract, brought her to Hollywood, gave her $100 a week, and began to manage her career. Hawks changed her name to Lauren Bacall. Nancy Hawks took Bacall under her wing. She dressed the newcomer stylishly, and guided her in matters of elegance, manners, and taste. Bacall's voice was trained to be lower, more masculine, and sexier, which resulted in one of the most distinctive voices in Hollywood. In the movie, Bacall takes on Nancy's nickname “Slim”.

Breakthrough

During screen tests for To Have and Have Not (1944), Bacall was nervous. To minimize her quivering, she pressed her chin against her chest and to face the camera, tilted her eyes upward. This effect became known as "The Look", Bacall's trademark.

On the set, Humphrey Bogart, who was married to Mayo Methot, initiated a relationship with Bacall some weeks into shooting and they began seeing each other.

On a visit to the National Press Club in Washington, D.C. on February 10, 1945, Bacall's press agent, chief of publicity at Warner Bros. Charlie Enfield, asked the 20-year-old Bacall to sit on the piano which was being played by Vice-President of the United States Harry S. Truman. The photos caused controversy and made worldwide headlines.

After To Have and Have Not, Bacall was seen opposite Charles Boyer in the critically-panned Confidential Agent (1945). Bacall would state in her autobiography that her career never fully recovered from this film, and that studio boss Jack Warner did not care about quality. She then appeared with Bogart in the film noir The Big Sleep (1946), the thriller Dark Passage (1947), and John Huston's melodramatic suspense film Key Largo (1948). She was cast with Gary Cooper in the adventure tale Bright Leaf (1950).

1950s

Bacall turned down scripts she did not find interesting and thereby earned a reputation for being difficult. Yet, for her leads in a string of films, she received favorable reviews. In Young Man with a Horn (1950), co-starring Doris Day and Kirk Douglas, Bacall played a two-faced femme fatale, with more than a hint of lesbianism to her character.