The current world number one faced a former top-ranked star on Thursday and Victoria Azarenka made Naomi Osaka feel like the underdog.
Victoria Azarenka looked set to cause an upset at the French Open but fell to defeat from a set and a break up versus top seed Naomi Osaka.
It is three French Open first-round exits in four years for Jelena Ostapenko, as the 2017 champion's odd Roland Garros record continued.
Johanna Konta celebrated her 28th birthday by reaching the semi-finals of the Internazionali d'Italia in Rome on Friday.
While Simona Halep insisted fitness was not an issue ahead of the French Open, Naomi Osaka eased through at the Internazionale d'Italia.
Elina Svitolina's hopes of securing a third successive title in Rome were ended by Victoria Azarenka following Serena Williams' withdrawal.
Serena and Venus Williams will meet in the second round at the Foro Italico, 21 years after their only other clash in Rome.
Defending champion Petra Kvitova made it through to the third round in Madrid along with the likes of Sloane Stephens and Ashleigh Barty.
Caroline Wozniacki's participation in the Madrid Open was brief, while Elina Svitolina suffered an early exit on day two.
Petra Kvitova, aiming to become the first woman to win a Premier Mandatory tournament four times, was too good for Sofia Kenin in Madrid.