Unbothered by that reaction Wednesday night -- or by the criticism he received from Andy Murray after taking breaks while beating him two days earlier -- Tsitsipas pointed out that he is doing nothing that violates any regulation.
Which is true. The Grand Slam rulebook just says players should take a "reasonable'' amount of time but does not provide an exact number of minutes that would be acceptable.
"If I break a rule, sure, I'm guilty. I agree; I'm not doing something right," Tsitsipas said after hitting 27 aces and beating Mannarino 6-3, 6-4, 6-7 (4), 6-0 with the roof closed at Arthur Ashe Stadium because of heavy rain from the remnants of Hurricane Ida. "If I'm staying within the guidelines, then what's the issue?''
On Wednesday, Tsitsipas took a toilet break that created an eight-minute delay between the end of the third set and start of the fourth. His return was greeted by fans voicing their displeasure, certainly aware that three-time major champion Murray decried what he called "nonsense'' by the 23-year-old from Greece.
Murray also said he "lost respect" for Tsitsipas, who is seeded No. 3 at Flushing Meadows and was the runner-up at the French Open in June.
Tsitsipas said he feels refreshed after he heads off the court to change his clothing.
Asked about the spectators' boos, he replied: "I haven't done anything wrong, so I don't understand. The people love the sport; they come to watch tennis. I have nothing against them. I love the fans. But some people don't understand. That's all. They don't understand. They haven't played tennis at high level to understand how much effort and how much difficult it is to do what we are doing. Sometimes we need a short break to do what we have to do."
Mannarino, who got some tennis balls and practiced serves to keep his shoulder loose while his opponent was away before the fourth set, agreed that the fault lies with the rulebook, not Tsitsipas.
"He's not doing anything wrong,'' the French player said. "I think the rule is wrong.''
The US Open is the only Grand Slam tournament where Tsitsipas has yet to reach the fourth round. He has been that far at Wimbledon and to the semifinals at the Australian Open, in addition to his run at Roland Garros before losing to Novak Djokovic in the final.
Now, Tsitsipas will face 18-year-old Carlos Alcaraz of Spain for a berth in the fourth round.
"I want to play the best of my game against him,'' Tsitsipas said. "I see him as a potential contender in the future for Grand Slam titles and other big events.''
In other men's competition, 11th-seeded Diego Schwartzman eliminated 2017 runner-up Kevin Anderson in a match that started on one court before 7:30 p.m. and finished on another just past 1 a.m. after an interruption caused by the rain and winds.
Schwartzman won 7-6 (4), 6-3, 6-4 to reach the third round.
They started at Louis Armstrong Stadium, which has a retractable roof, but the openings created for natural ventilation allowed rain to blow onto the court. So, play was paused at 5-5 in the first set so the surface could be dried. After they resumed, the puddles grew too large at the outset of the second set, so the action was halted again.
Armstrong was deemed unplayable, so the match was moved to Ashe, where they were able to pick things up again after a break of nearly 2½ hours while another match finished.
The Associated Press contributed to this report.