Tenth seed Victoria Azarenka suffered a shock straight-set defeat by world number 161 Anna Karolina Schmiedlova in the French Open second round.
The Belarusian, 31, reached the US Open final earlier this month but struggled on the clay against Schmiedlova, who won 6-2 6-2.
The Slovak fell in the second set and the trainer was needed to treat her knee, but it did not halt her progress.
Top seed Simona Halep and third seed Elina Svitolina both won their matches.
Halep, who won her first Grand Slam title at the 2018 Roland Garros, beat fellow Romanian Irina Camelia Begu in a 6-3 6-4 success.
Fresh from winning the Italian Open title earlier this week, 29-year-old Halep demonstrated why she is considered the favourite in Paris with a clean performance to earn her 15th straight win.
Halep will face 25th seed Amanda Anisimova in the third round, giving her the chance to avenge defeat by the American teenager in last year’s quarter-finals.
Anisimova, 19, teed up the rematch with a 6-2 6-0 win over fellow American Bernarda Pera.
Ukraine’s Svitolina regained her composure after being bagelled in the second set to claim a 6-3 0-6 6-2 victory over Mexican qualifier Renata Zarazua.
“I was trying to get back into the match,” said the 26-year-old. “I lost my way a bit and was making too many errors.”
Svitolina won her 15th WTA title in Strasbourg last week but is yet to reach a Grand Slam final.
She will face Russian world number 31 Ekaterina Alexandrova next.
A possible meeting with Serena Williams in the quarter-finals is no longer on the cards after the American 23-time Grand Slam champion withdrew before her second-round match with an Achilles injury.