Tsitsipas is the son of a Greek father, Apostolos Tsitsipas and a Russian mother, former pro-tennis player Julia Apostoli. His grandfather, Sergei Salnikov, was a Soviet football player and manager.
Tsitsipas is a former world number one junior tennis player. His junior highlights include winning the Trofeo Bonfiglio, a 'Grade A' event in Milan, Italy. He is the winner of the Boys' Doubles at the 2016 Wimbledon Championships together with Kenneth Raisma, thus becoming the second male Greek tennis player to win a Grand Slam title at any division and the first one in the Open Era, with the first male Greek tennis player in history to win a Grand Slam title being Nicky Kalogeropoulos, the winner of the 1963 Roland Garros and Wimbledon boys' singles tournaments.
On April 29, 2018 Tsitsipas played his first ever ATP-final in Barcelona, losing 6-2, 6-1 to defending champion and worlds #1 Rafael Nadal. On August 12, 2018 Tsitsipas reached his second final in Montréal losing again to Rafa Nadal with 2-0 (6-2 and 7-6) in sets. On October 21, 2018 Tsitsipas won his first ATP-title beating qualifier Ernests Gulbis from Latvia 6-4, 6-4 in Stockholm in his third final.
Tsitsipas won the final of the Next Gen Finals in Milan on November 11, 2018. His opponent was Alex de Minaur from Australia. This Next Gen tournament is for the best players in the ATP-ranking 21 years old or younger.
In January 2019 Tsitsipas reached (as the first Greek tennis-player ever) to the semi final of the Australian Open, one of the four Grand Slam tournaments. Once again Rafa Nadal was the man who stopped him from bigger success. Biggest scalp of Tsitsipas in his run to the semifinal was Roger Federer, winner of 20 Grand Slam single titles.