As of 2009, Day was the top-ranking female box office star of all time and ranked sixth among the top ten box office performers (male and female).

Doris Day was born in the Cincinnati, Ohio, neighborhood of Evanston to Alma Sophia Welz (a housewife) and Wilhelm (later William) Kappelhoff (a music teacher and choir master). All of her grandparents were German immigrants. Although the 1930 census lists her at age 7, she states to her biographer in "Doris Day: Her Own Story" that she was born in 1924. Specifically she states, "[I was] named by my mother in honor of her favorite actress, Doris Kenyon, a silent screen star of that year 1924." The youngest of three children, she had two brothers: Richard, who died before she was born, and Paul, a few years older.

Her parents' marriage failed due to her father's reported infidelity. Although the family was Roman Catholic, her parents divorced. After her second marriage, Day herself would become a Christian Scientist. Day was married four times.

Day developed an early interest in dance, and in the mid-1930s formed a dance duo with Jerry Doherty that performed locally in Cincinnati. A car accident on October 13, 1937 damaged her legs and curtailed her prospects as a professional dancer. While recovering, Day took singing lessons, and at 17 she began performing locally.

It was while working for local bandleader Barney Rapp in 1939 or 1940 that she adopted the stage name "Day" as an alternative to "Kappelhoff," at his suggestion. Rapp felt her surname was too long for marquees. The first song she had performed for him was Day After Day, and her stage name was taken from that. After working with Rapp, Day worked with a number of other bandleaders including Jimmy James, Bob Crosby, and Les Brown. It was while working with Brown that Day scored her first hit recording, "Sentimental Journey", which was released in early 1945. It soon became an anthem of the desire of World War II demobilizing troops to return home. This song is still associated with Day, and was rerecorded by her on several occasions, as well as being included in her 1971 television special.

While singing with the Les Brown band and briefly with Bob Hope, Day toured extensively across the United States. Her popularity as a radio performer and vocalist, which included a second hit record My Dreams Are Getting Better All the Time, led directly to a career in films. Already in 1941 Day appeared as a singer with the Les Brown band in a soundie (a Cinemasters production). After her separation from her second husband, George Weidler, in 1948, Day reportedly intended to leave Los Angeles and return to her mother's home in Cincinnati. Her agent Al Levy convinced her to attend a party at the home of composer Jule Styne. Her personal circumstances at the time and her reluctance to perform contributed to an emotive performance of Embraceable You, which greatly impressed Styne and his partner, Sammy Cahn. They then recommended her for a role in Romance on the High Seas which they were working on for Warner Brothers. The withdrawal of Betty Hutton due to pregnancy left the main role to be re-cast, and Day got the part.

The film provided her with another hit recording It's Magic. In 1950 U.S. servicemen in Korea voted her their favorite star. She continued to make minor and frequently nostalgic period musicals such as Starlift, On Moonlight Bay, By the Light of the Silvery Moon, and Tea For Two for Warner Brothers. In 1953 Day appeared as Calamity Jane, winning the Academy Award for Best Original Song for Secret Love (her recording of which became her fourth U.S. No. 1 recording).

After filming Young at Heart (1954) with Frank Sinatra, Day chose not to renew her contract with Warner Brothers. She elected to work under the advice and management of her third husband, Marty Melcher, whom she married in Burbank on her 29th birthday (April 3, 1951). Day had divorced saxophonist-songwriter George W. Weidler (born September 11, 1917, died July 26, 1995) on May 31, 1949 in Los Angeles in an uncontested divorce action after marrying him on March 30, 1946 in Mount Vernon, New York, separating in April 1947 and filing for divorce in June 1948.

Day subsequently took on more dramatic roles, including her 1954 portrayal of singer Ruth Etting in Love Me or Leave Me. Day would later call it, in her autobiography, her best film. She was also paired with such top stars as Jack Lemmon, James Stewart, Cary Grant, David Niven, and Clark Gable.

In Alfred Hitchcock's The Man Who Knew Too Much (1956), Day sang "Que Sera, Sera (Whatever Will Be, Will Be)" which won an Academy Award for Best Original Song and became her signature song. According to Jay Livingston, who wrote the song with Ray Evans, Day preferred another song used briefly in the film, "We'll Love Again" and skipped the recording for Que Sera, Sera. At the studio's insistence she relented. After recording the number, she reportedly told a friend of Livingston, "That's the last time you'll ever hear that song". However, the song was used again in Please Don't Eat the Daisies (1960), and was reprised as a brief duet with Arthur Godfrey in The Glass Bottom Boat (1966). Que Sera, Sera also became the theme song for her CBS television show (1968–73). The Man Who Knew Too Much was her only film for Hitchcock and, as she admitted in her 1975 autobiography, she was initially concerned at his lack of direction. She finally asked if anything was wrong and Hitchcock said everything was fine — if she weren't doing what he wanted, he would have said something.