Jessica Pegula became the highest-ranked women's player to exit the 2023 French Open to date as she was emphatically beaten by Elise Mertens.
American third seed Pegula, a quarter-finalist in Paris last year, struggled in a 6-1 6-3 defeat.
Belgian 28th seed Mertens will face a Russian, either Anastasia Potapova or Anastasia Pavlyuchenkova, next.
Pegula's time at Roland Garros is not over as she is through to the women's doubles second round with Coco Gauff.
The pair reached the final in 2022, and the semi-finals at the Australian Open earlier this year.
Pegula, whose preparations for the French Open were derailed by food poisoning, is the 21st seed to exit the women's singles inside six days of action.
Friday proved a much easier day for Belarusian world number two Aryna Sabalenka, however, as she comfortably defeated Russian Kamilla Rakhimova 6-2 6-2.
Sabalenka, crowned Australian Open champion in January, will take on American Sloane Stephens or Kazakhstan's Yulia Putintseva in the fourth round.
Ninth seed Daria Kasatkina also progressed, making light work of American Peyton Stearns in a 6-0 6-1 win.
The Russian will face compatriot Anna Blinkova or Ukraine's Elina Svitolina next.