A natural athlete, as a boy Newcombe played several sports until devoting himself to tennis. He was the Australian junior champion in 1961, 1962 and 1963 and became a member of Australia's Davis Cup winning team in 1964. He won his first Grand Slam major in 1965 by taking the Australian Championships doubles title with fellow Australian Tony Roche. That same year, the duo won the Wimbledon doubles title. They would team up to win the Australian doubles championship three more times, Wimbledon another four times and the US Championships in 1967, the French Championships in 1967 and 1969. Together, Newcombe and Roche won 12 Grand Slam titles, more than any other men's team in tennis history.

Newcombe's powerful serve and volley was the backbone of his attacking game. To the delight of fans, and the surprise of his opponent, he frequently came up with a second-serve ace. His play made him the No. 1 amateur in the world in 1967. As a pro, he was the world number one player in 1970, 1971 and 1973. In singles play, he was a two time winner of the Australian Open, a three time winner of Wimbledon, and the US Open twice.

As member of Lamar Hunt's, "World Championship Tennis" professional tour group, and part of the players union, he was banned by the International Tennis Federation from competing in the 1972 Wimbledon championships and he boycotted the event in 1973. Very popular with the fans, Newcombe's absence resulted in urgent negotiations that ultimately resolved the issues. He served as President of the Association of Tennis Professionals in 1977 and 1978.

Newcombe and Rod Laver are the only players to ever win both the US Open and Wimbledon men's singles titles as an amateur and as a professional. The grass surfaces favored his game and although he made it to the 1964 finals, the French Open's clay surface was the only major singles championship he never won. However, he did take the French doubles title on three occasions. Overall, he won 25 Grand Slam major titles in singles, doubles, and mixed doubles.

John Newcombe was the last of the Australians who dominated tennis in the 1950s and 1960s. In his 1979 autobiography Jack Kramer, the long-time tennis promoter and great player himself, included Newcombe in his list of the 21 greatest players of all time[1] In 1986, his achievements were recognized with his induction into the International Tennis Hall of Fame. Still active in tennis, he was made captain of Australia's Davis Cup team in 1995.

Notoriously, he was revealed to be President George W. Bush's drinking companion on the night when he was charged with driving under the influence. This controversy surfaced during the 2000 US Presidential Election.