David Paradine Frost was born in Tenterden, Kent, on 7 April 1939, the son of a Methodist minister of Huguenot descent, the Rev. Wilfred John "W. J." Paradine Frost, and his wife, Mona (Aldrich); he had two elder sisters. While living in Gillingham, Kent, he was taught in the Bible class of the Sunday school at his father's church (Byron Road Methodist) by David Gilmore Harvey, and subsequently started training as a Methodist local preacher, which he did not complete.

Frost studied at Gonville & Caius College, Cambridge, from 1958, graduating with a Third in English. He was Editor of both the university's student paper, Varsity, and the literary magazine Granta. He was also secretary of the Footlights Drama Society, which included actors such as Peter Cook and John Bird. During this period, Frost appeared on television for the first time in an edition of Anglia Television's Town And Gown, performing several comic characters. "The first time I stepped into a television studio", he once remembered, "it felt like home. It didn't scare me. Talking to the camera seemed the most natural thing in the world."

Frost was known for several relationships with high-profile women. In the mid-1960s, he dated British Actress Janette Scott, between her marriages to Songwriter Jackie Rae and singer Mel Tormé; in the early 1970s he was engaged to American Actress Diahann Carroll; between 1972 and 1977 he had a relationship with British socialite Caroline Cushing; in 1981 he married Lynne Frederick, widow of Peter Sellers, but they divorced the following year. He also had an 18-year intermittent affair with American Actress Carol Lynley.

Frost was chosen by Writer and Producer Ned Sherrin to host the satirical programme That Was the Week That Was, alias TW3 after Frost's flatmate John Bird suggested Sherrin should see his act at The Blue Angel. The series, which ran for less than 18 months during 1962–63, was part of the satire boom in early 1960s Britain and became a popular programme.

An American version of TW3 ran after the original British series had ended. Following a pilot episode on 10 November 1963, the 30-minute US series, also featuring Frost, ran on NBC from 10 January 1964 to May 1965. In 1985, Frost produced and hosted a television special in the same format, That Was the Year That Was, on NBC.

Frost was the only person to have interviewed all eight British prime ministers serving between 1964 and 2014 (Harold Wilson, Edward Heath, James Callaghan, Margaret Thatcher, John Major, Tony Blair, Gordon Brown and David Cameron) and all seven US Presidents in office between 1969 and 2008 (Richard Nixon, Gerald Ford, Jimmy Carter, Ronald Reagan, George H. W. Bush, Bill Clinton and George W. Bush).

Frost fronted various programmes following the success of TW3, including its immediate successor, Not So Much a Programme, More a Way of Life, which he co-chaired with Willie Rushton and poet P. J. Kavanagh. Screened on three evenings each week, this series was dropped after a Sketch was found to be offensive to Catholics and another to the British royal family. More successful was The Frost Report, broadcast between 1966 and 1967. The show launched the television careers of John Cleese, Ronnie Barker and Ronnie Corbett, who appeared together in the Class Sketch.

Frost was a member of a successful consortium, including former executives from the BBC, which bid for an ITV franchise in 1967. This became London Weekend Television, which began broadcasting in July 1968. The station began with a programming policy which was considered 'highbrow' and suffered launch problems with low audience ratings and financial problems. A September 1968 meeting of the Network Programme Committee, which made decisions about the channel's scheduling, was particularly fraught, with Lew Grade expressing hatred of Frost in his presence. Frost, according to Kitty Muggeridge in 1967, had "risen without a trace."

In 1968 he signed a contract worth £125,000 to appear on American television in his own show on three evenings each week, the largest such arrangement for a British television personality at the time. From 1969 to 1972, Frost kept his London shows and fronted The David Frost Show on the Group W (U.S. Westinghouse Corporation) television stations in the United States. His 1970 TV special, Frost on America, featured guests such as Jack Benny and Tennessee Williams.

He was involved in the station's early years as a presenter. On 20 and 21 July 1969, during the British television Apollo 11 coverage, he presented David Frost's Moon Party for LWT, a ten-hour discussion and entertainment marathon from LWT's Wembley Studios, on the night Neil Armstrong walked on the moon. Two of his guests on this programme were British Historian A. J. P. Taylor and entertainer Sammy Davis, Jr. Around this time Frost interviewed Rupert Murdoch whose recently acquired Sunday newspaper, the News of the World, had just serialised the memoirs of Christine Keeler, a central figure in the Profumo scandal of 1963. For the Australian publisher, this was a bruising encounter, although Frost said that he had not intended it to be. Murdoch confessed to his biographer Michael Wolff that the incident had convinced him that Frost was "an arrogant bastard, [and] a bloody bugger".

In a declassified transcript of a 1972 telephone call between Frost and Henry Kissinger, President Nixon's National Security Advisor and Secretary of State, Frost urged Kissinger to call chess grandmaster Bobby Fischer and urge him to compete in that year's World Chess Championship. During this call, Frost revealed that he was working on a novel.

Frost taped around 29 hours of interviews with Nixon over a period of four weeks. Nixon, who had previously avoided discussing his role in the Watergate scandal which had led to his resignation as President in 1974, expressed contrition saying "I let the American people down and I have to carry that burden with me for the rest of my life".

Frost/Nixon was originally a play written by Peter Morgan, developed from The Nixon Interviews which Frost had conducted with Richard Nixon in 1977. Frost/Nixon was presented as a stage production in London in 2006, and on Broadway in 2007. The play was adapted into a Hollywood motion picture starring Michael Sheen as Frost and Frank Langella as Nixon, both reprising their stage roles. The film was directed by Ron Howard and released in 2008. It was nominated for five Golden Globe awards: Best Motion Picture Drama, Best Director, Best Actor, Best Screenplay and Best Original Score, and for five Academy Awards: Best Picture, Best Actor, Best Director, Best Adapted Screenplay and Best Editing.

Frost was an organiser of the Music for UNICEF Concert at the United Nations General Assembly in 1979. Ten years later, he was hired as the anchor of the new American tabloid news program Inside Edition. He was dismissed after only three weeks, due to poor ratings. It seems he was "considered too high-brow for the show's low-brow format." ABC News reporter Bill O'Reilly was recruited as his replacement.

On 19 March 1983, Frost married Lady Carina Fitzalan-Howard, daughter of the 17th Duke of Norfolk. Over the next five years, they had three sons and for many years lived in Chelsea, with their weekend home at Michelmersh Court in Hampshire.

Frost hosted Through the Keyhole, which ran on several UK channels from 1987 until 2008 and also featured Loyd Grossman. Produced by his own production company, the programme was first shown in prime time and on daytime television in its later years.

Frost was one of the "Famous Five" who launched TV-am in February 1983 but, like LWT in the late 1960s, the station began with an unsustainable "highbrow" approach. Frost remained a presenter after restructuring. Frost on Sunday began in September 1983 and continued until the station lost its franchise at the end of 1992. Frost had been part of an unsuccessful consortium, CPV-TV, with Richard Branson and other interests, which had attempted to acquire three ITV contractor franchises prior to the changes made by the Independent Television Commission in 1991. After transferring from ITV, his Sunday morning interview programme Breakfast with Frost ran on the BBC from January 1993 until 29 May 2005. For a time it ran on BSB before moving to BBC 1.

After having been in television for 40 years, Frost was estimated to be worth £200 million by the Sunday Times Rich List in 2006, a figure he considered a significant over-estimate in 2011. The valuation included the assets of his main British company and subsidiaries, plus homes in London and the country.

In 2007, Frost hosted a discussion with Libya's leader Muammar Gaddafi as part of the Monitor Group's involvement in the country. In June 2010, Frost presented Frost on Satire, an hour-long BBC Four documentary looking at the history of television satire.

In February 2009, Frost was featured on the Australian Broadcasting Corporation's international affairs programme Foreign Correspondent in a report titled "The World According To Frost", reflecting on his long career and portrayal in the film Frost/Nixon.

On 31 August 2013, Frost was aboard a Cunard Line cruise ship, the MS Queen Elizabeth 2, when he had a heart attack and died. Cunard said that the vessel had left Southampton for a ten-day cruise in the Mediterranean, ending in Rome. The then British Prime Minister David Cameron paid tribute, saying: "He could be—and certainly was with me—both a friend and a fearsome interviewer." Michael Grade commented: "He was kind of a television renaissance man. He could put his hand to anything. He could turn over Richard Nixon or he could win the comedy prize at the Montreux Golden Rose festival." On 13 March 2014, a Service was held at Westminster Abbey, at which Frost was honoured with a memorial stone in Poets' Corner. His post-mortem found that he had hypertrophic cardiomyopathy, his 31-year-old son Miles Frost died from the same condition in 2015.