The finalist in 2021 sent more than 30 winners to wrap up the match in just 91 minutes, setting up a meeting with Italian Matteo Arnaldi, who stunned sixth seed Andrey Rublev earlier on Friday.
Zhang became the first Chinese man in 86 years to win a main-draw match at Roland Garros last year en route to the third round, but could not improve on that showing as he was never able to set up a break-point chance.
The ninth-ranked Tsitsipas came charging out of the gate, winning the first three games, and kept up the momentum as he broke Zhang on his second try in the opening game of the second set.
Tsitsipas played pristine tennis, producing just three unforced errors in the second set, as he broke Zhang again in the ninth game.
Zhang struggled with his forehand late in the match and sent shots out of bounds on back-to-back points to hand Tsitsipas the break in the fourth game of the third set, and the Greek ran away with it from there.