Defending Roland Garros champion Jelena Ostapenko lost in the first round on Sunday 7-5, 6-3 to Ukraine's Kateryna Kozlova on Court Philippe Chatrier.
The British No. 1 has never won a match in Paris in four appearances in the main draw.
"I made like 50 unforced errors and so many double faults".
"It was bad day", she told reporters afterwards.
Also back: two-time champion Maria Sharapova, in the draw for the first time since 2015, after missing 2016 because of a doping suspension and 2017 because the tournament denied her a wild-card entry; and former No. 1 Victoria Azarenka, who missed the tournament past year after giving birth to a son.
"Any player who could hit, like, five shots back, I think, probably could beat me today, because I didn't really play well", said Ostapenko, who complained about limited preparation ahead of Roland Garros because of a leg injury suffered at the Italian Open this month.
US Open champion Sloane Stephens was clearly in a hurry, dropping just two games in a 6-2 6-0 win over Arantxa Rus of Holland.
Seven-time Grand Slam singles victor Williams hit back in the second set, racing into an early 3-0 lead, but Wang came back into contention with three games of her own in a row.
The 22 year-old became the third casualty in a day of upsets that also saw veteran Venus Williams and British star, Johanna Konta ousted from the championship.
Tennis fans will have to wait a bit longer to see Rafael Nadal open his bid for a record 11th title at Roland Garros as the first day of the French Open 2018 does not feature the Spaniard.
France's Alize Cornet is through to the second round of the French Open, beating 2012 runner-up Sara Errani of Italy 2-6, 6-2, 6-3.
Two matches have been left unfinished at the French Open as play was suspended Sunday night due to darkness. We don't. We just try to play and win each point, each game.
Seven-time Grand Slam champion Venus Williams lost to world number 91 Wang Qiang in the first round of the French Open.
She contributed 13 double faults amid 48 unforced errors to tumble out 7-5 6-3 to the world number 66.
Dimitrov had been drawn to face experienced Viktor Troicki in the tournament opener on Philippe Chatrier Court.
Kyrgios's withdrawal meant that eight places in the first round were opened up to lucky losers.
The match ended with a score of 7-5, 6-3 and lasted an hour and 34 minutes.
Venus Williams and rain are on the schedule as the year's second Grand Slam tournament is set to start at Roland Garros. There are no ideal days in tennis.
Instead, the in-form Alexander Zverev, who is seeded second, will be the highest seed in action in the men's singles draw. "I think her game just got better and better during the match".