Elina Svitolina became the seventh top-10 seed to be knocked out in the French Open’s opening week as she fell in the third round to Barbora Krejcikova.
Fifth seed Svitolina was outclassed 6-3 6-2 by the impressive unseeded Czech.
The Ukrainian follows Ashleigh Barty, Naomi Osaka, Karolina Pliskova, Aryna Sabalenka, Belinda Bencic and Bianca Andreescu out of Roland Garros.
However, defending champion Iga Swiatek and fourth seed Sofia Kenin advanced, alongside American teenager Coco Gauff.
Gauff, 17, had taken the first set 6-1 against compatriot Jennifer Brady before the 13th seed called for medical assistance and then retired in tears. It was not immediately clear what the injury was but she has struggled with a foot injury in recent weeks.
American Kenin, the 2020 runner-up and highest seed remaining in the tournament, looked in danger of joining the casualty list when she lost the opening set from 3-0 up by surrendering three successive service games to compatriot Jessica Pagula.
But her aggressive approach ultimately paid off against a more passive Pagula as Kenin hit 48 winners to triumph 4-6 6-1 6-4 in a mixed display that also featured 41 unforced errors and 10 double faults.
Swiatek, meanwhile, made a wobbly start against Estonian 30th seed Anett Kontaveit by dropping her opening service game but recovered to take the first set to a tie-break, which she dominated. A 55-minute opening set made way for a swift second where the 20-year-old Pole did not drop a game, taking a 7-6 (7-4) 6-0 victory.
Swiatek and Kenin are two of just three top-10 seeds left standing, along with Serena Williams, who reached the fourth round on Friday,.
Krejcikova, until recently a doubles specialist with two Grand Slam titles to her name in that format, produced arguably the performance of the round in her victory over Svitolina, 26.
The 25-year-old, who won her maiden singles title in Strasbourg last month, never looked back after holding her serve in a mammoth 21-minute game at 4-3 up in the first set, breaking Svitolina in each game either side.
She next faces former US Open champion and 2018 French Open runner-up Sloane Stephens in the last 16 after the unseeded American beat 18th seed Karolina Muchova 6-3 7-5.
Both players struggled for accuracy throughout, Stephens hitting 25 unforced errors and Muchova 32, but the 28-year-old American broke serve early in the first set and, crucially, at 5-5 in the second, to progress.