Doris Day was born in Evanston, a neighborhood within the city of Cincinnati, Ohio, USA to Alma Sophia Welz and William/Wilhelm von Kappelhoff. All four of her grandparents were German immigrants, and at least one ancestor was Dutch.

Her parents' marriage failed due to her father's infidelities, some of which Day witnessed taking place in the family home. Though the family was Roman Catholic, her parents divorced. After her second marriage, Day herself would become a Christian Scientist. As of 2008, Day has been married four times.

The youngest of three children, she had two brothers: Richard, who died before she was born, and Paul, a few years older. She was named after silent movie actress Doris Kenyon, whom her mother admired.

Growing up in the 1930s, Day developed an interest in dance. By the mid-1930s, she formed a dance duo that performed locally in Cincinnati, until a car accident on October 13, 1937 damaged her legs and curtailed her prospects as a professional dancer. However, while recovering, Day took up singing. Soon she began to take lessons, and at the age of 17 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 re-recorded by her on several occasions, as well as being included in her 1971 television special.

During her time with Les Brown, and a brief stint with Bob Hope, Day toured extensively across the United States. Her popularity as a radio performer and vocalist, including a second hit record My Dreams Are Getting Better All The Time, led directly to a career in films. After her separation from second husband George Weidler in 1948, Day was set to leave Los Angeles and return to her mother's home in Cincinnati, when 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. Thus, Day began her film career, in 1948, in a "peppy" Hutton-esque role. (The film was digitally remastered and released on DVD in May 2007.)

The success of this film established her as a popular film personality, and provided her with another hit recording It's Magic. In 1950, U.S. servicemen in Korea voted her their favorite star. Early publicity saddled her with such unflattering nicknames as "The Tomboy with a Voice" and "The Golden Tonsil". 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, but 1953 found Day as pistol-packin' Calamity Jane in what has become one of Hollywood's most enduring musicals, 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, and instead freelanced under the management of her third husband, Martin Melcher, whom she married in Burbank on her 27th birthday, April 3, 1951 with the ceremony performed by Justice of the Peace Leonard W. Hamner.

Day had divorced saxophonist-songwriter George W. Weidler (*September 11, 1917 – †July 26, 1995) of Les Brown's band, brother of Virginia Weidler 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's first husband was trombonist-musician Albert Jorden (February 1, 1917 – July 1967) from Evanstown, Ohio, of Barney Rapp's Ohio-based band, and later of Jimmy Dorsey's band in New York, from March 1941 at City Hall in New York until their divorce in 1943.

Her range of acting broadened to include more dramatic roles. In 1955, she received some of the best notices of her career for her portrayal of singer Ruth Etting in Love Me or Leave Me, co-starring James Cagney. Doris would later call it, in her autobiography, her best film. She continued to be paired with some of Hollywood's top stars, including Jack Lemmon, James Stewart, Cary Grant, David Niven, and Clark Gable.

In Alfred Hitchcock's The Man Who Knew Too Much (1956), she sang Que Sera, Sera (Whatever Will Be, Will Be), which won an Academy Award for Best Original 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.

When the studio pushed her, she relented, but after recording the number in one take, she reportedly told a friend of Livingston's, "That's the last time you'll ever hear that song." The song was used again in her film, Please Don't Eat the Daisies (1960), and was reprised as a brief duet with Arthur Godfrey in The Glass Bottom Boat (1966). It also became the theme song for her television show (1968-1973).

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 wasn't doing what he wanted, he would have said something.

After the critical and popular success of Teacher's Pet, Day's popularity at the box office seemed to wane, and some critical attention focused on perceived elements of "blandness" in her on-screen persona, although in some foreign markets (Germany, Britain and the Commonwealth), she remained a top box office draw. A dynamic performance in The Pajama Game received warm critical notices, but box office returns were disappointing. In the case of The Tunnel of Love and It Happened to Jane, both the critical and popular response was uneven.

As a result, from 1957 to 1959, she was no longer regarded a "Top Ten Box Office Draw" by U.S. film exhibitors. This development may have been linked to a marked decline in popularity of musical films during the late 1950s, as well as to some poor choices in material made by Melcher on his wife's behalf. In addition, Day's popularity as a recording artist was diminished due to the growing popular taste for rock and roll. Que Sera, Sera, for instance, was never a No. 1 hit, being kept from the top by Elvis Presley's recording of Hound Dog.