3 in men's singles by the ATP, first achieved in August 2021, making him the highest-ranked Greek in tennis history, tied with Maria Sakkari.

[20] He did not win any singles finals that year, but he did have another runner-up finish at the Orange Bowl, this time losing to Miomir Kecmanović in a third set tiebreak.

[26] Tsitsipas's biggest title of the season came in doubles, when he partnered with Estonian player Kenneth Raisma to win his only junior Grand Slam event at Wimbledon.

[30] Tsitsipas began playing low-level ITF Futures events in Greece in 2013 shortly after turning 15, not long after he started competing on the junior tour.

[31] He qualified for his first event on the ATP Challenger Tour at the Burnie International in early 2015 while still 16 years old, but lost his only main draw match to Benjamin Mitchell.

[35] Tsitsipas played in his first ATP main draw at the 2017 Rotterdam Open, where he lost his debut match to the eventual champion Jo-Wilfried Tsonga.

[45][46] Tsitsipas's first breakthrough of the year came at the Barcelona Open during the clay court season, where he reached his first career ATP final without dropping a set.

[49] Tsitsipas closed out the clay court season by winning his first career Grand Slam match at the French Open against Carlos Taberner before losing to Thiem, the eventual runner-up.

[64] Tsitsipas began the season at the Hopman Cup alongside Maria Sakkari, making them the first team to represent Greece at the event in 17 years.

[67][68] At the 2019 Australian Open, Tsitsipas reached his first major semifinal, despite having won just five Grand Slam singles matches in total the previous year.

3 and defending champion Roger Federer in the fourth round, saving all twelve of the break points he faced in a rematch of their Hopman Cup encounter earlier in the month.

[74] Tsitsipas closed out the early year hard court season with a career-best result in doubles, finishing runner-up to the Bryan brothers at the Miami Open with Wesley Koolhof.

He was eliminated from the season ending event with a 1–2 record during the round-robin portion of the competition, having defeated Andrey Rublev, but losing to Dominic Thiem and Rafael Nadal.

In the quarterfinals, Tsitsipas became only the second player along with Fabio Fognini at the 2015 US Open to beat Rafael Nadal in a grand slam match from two sets to love down.

[104][105] At the 2021 BNP Paribas Open he reached the quarterfinals, beating Pedro Martínez, Fabio Fognini and Alex de Minaur before losing to Nikoloz Basilashvili.

[109] Tsitsipas became the first man born in 1998 or later to get 200 career tour-level wins after defeating Laslo Đere in the first round at the Abierto Mexicano Telcel tournament.

[128] At the Australian Open, Tsitsipas defeated Quentin Halys, Rinky Hijikata, Tallon Griekspoor, Jannik Sinner, Jiří Lehečka, and Karen Khachanov on his way to his second Grand Slam final.

In the summer grass season, he received wildcards for Stuttgart,[130] Halle,[131] and at the Mallorca Championships where he was the defending champion; he won one match across these tournaments.

[135] In August, he won his tenth title at the Los Cabos Open, defeating John Isner, Nicolás Jarry, Borna Ćorić, and Alex de Minaur in straight sets in the final.

In his fifth consecutive appearance at the ATP Finals, Tsitsipas lost to Jannik Sinner in straight sets and retired mid-way through his match against Holger Rune before withdrawing from the event due to a back injury.

[141] In Melbourne, where Tsitsipas was defending finalist points, he reached the round of 16 with wins against Zizou Bergs, Jordan Thompson, and Luca Van Assche.

After participating in play-offs for Davis Cup World Group 1 in Athens where he won against Marius Copil of Romania,[142] he began his title defence at Los Cabos.

He defeated Tomás Martín Etcheverry, Alexander Zverev, and Karen Khachanov, all in straight sets, to reach the semi-final where he met Jannik Sinner.

[154] He followed this match by announcing the end of his coaching partnership with his father, Apostolos, citing desires to maintain healthier boundaries between tennis and his family.

[157] In his next match at the Laver Cup in Berlin, Tsitsipas won comprehensively against Kokkinakis in straight sets before going on to win the event with Team Europe.

His run in Shanghai included straight sets wins against Kei Nishikori and Alexandre Müller before ending with a fourth round defeat to Danill Medvedev.

[159] His European indoor season included quarterfinal runs in Antwerp and Basel, losing to Jiří Lehečka and Arthur Fils, respectively.

In the final Masters 1000 tournament of the year, Tsitsipas reached the quarterfinals with wins over Roberto Carballes Baena, Alejandro Tabilo, and Francisco Cerundolo to set up a rematch with Alexander Zverev.

[160] As a result, Tsitsipas failed to accrue enough points to directly qualify for the ATP Finals for the first time in six years, becoming the second alternate behind Grigor Dimitrov.

[10][186] His maternal grandfather Sergei Salnikov was an Olympic gold medal-winning member of the Soviet national football team and a former manager of FC Spartak Moscow.