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. He also made his Grand Slam debut later that year as a qualifier at the French Open, but lost to Ivo Karlović in his first match. After losing in qualifying at the US Open, Tsitsipas won his first Challenger title in Genova. Overall, he qualified for a tour-best eight events during the season, including Wimbledon and the Shanghai Masters. However, he did not win a tour-level match until the very end of the season when he defeated fellow Next Gen player Karen Khachanov in Shanghai. At the European Open in Belgium the following week, Tsitsipas reached his first ATP semifinal as a qualifier. During the event, he upset hometown favorite and world No. 10 David Goffin for his first career top 10 victory. With this run, Tsitsipas became the first Greek player to be ranked in the top 100 of the ATP rankings, accomplishing the feat at the age of 19. He also reached a high enough ranking to be named an alternate for the Next Gen ATP Finals. Tsitsipas closed out the season with another Challenger final, this time in Brest.