(CNN) If Novak Djokovic entered the French Open with plenty of question marks hanging over his form he departs Paris still searching for answers after suffering his first straight-set grand slam defeat since the 2013 Wimbledon final.

Dominic Thiem crushed Roland Garros' defending champion 7-6 (7-5) 6-3 6-0 in the quarterfinals on a sunny, blustery Wednesday, a result that means the Serb will also tumble out of the top two in the rankings for the first time since early 2011.

Thiem must now upend familiar foe Rafael Nadal -- who progressed when Pablo Carreno Busta retired while trailing 6-2 2-0 -- to make a maiden grand slam final.

World No. 1 Andy Murray and 2015 winner Stan Wawrinka will square off in the semifinals for the second straight year after the Scot eliminated Japan's Kei Nishikori 2-6 6-1 7-6 (7-0) 6-1 and the Swiss eased past Croatia's Marin Cilic 6-3 6-3 6-1.

Meanwhile, there was drama in the women's quarterfinals, as third-seed Simona Halep rallied from a 5-1 second-set deficit and saved a match point to overcome fifth-seed Elina Svitolina 3-6 7-6 (8-6) 6-0.

Karolina Pliskova, the second seed, claimed a marathon first set on the way to beating the last French player remaining in singles, Caroline Garcia, 7-6 (7-3) 6-4.

If Pliskova ousts Halep on Thursday, the Czech will replace Angelique Kerber as the women's No. 1.

'Pretty bad'

That Thiem ousted Djokovic wasn't a huge surprise -- after all the seventh-ranked Austrian trails only Nadal in match wins in 2017 and is tied for first with the Spaniard in clay-court victories this season.

But the manner in which Djokovic -- who teamed up with new coach Andre Agassi last month -- crumbled in the third set will be particularly worrying for his fans.

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It's worrying too for Djokovic, who blew a 4-2 lead in the first set.

Only 12 months ago he put the exclamation mark on one of the most dominant spells in tennis history, beating Murray in the final in Paris to become the first man in 47 years to claim four consecutive majors.

"It's hard to comment on the third set," he told reporters. "Obviously nothing was going my way and everything his way. Just a pretty bad set.

"It's a fact that I'm not playing close to my best, and I know that."

Djokovic's resounding victory over Thiem in the Rome semifinals last month might have been misleading, since the 23-year-old Austrian was coming off an emotional victory over Nadal 24 hours earlier.

Yet no one could have predicted Thiem to prevail in Paris so comfortably and one wonders what Agassi, not around for the match due to prior commitments, made of it all.

Don't blame Agassi

"Don't put Andre in the midst of this," said Djokovic, who slumped to a second-round loss against wildcard Denis Istomin at January's Australian Open. "This final set, of course, that's all me.

"As I have mentioned before several times when you guys ask me about his influence and impact on my game, it's gonna take time. It's not something that comes out in the first week. We have spent seven days together. We just got to know each other."

Djokovic said a break from the game wasn't out of the question yet also said he might change his grass-court plans by playing a Wimbledon warmup.

He insisted he was intent on getting things right.

"For me, it's a whole new situation that I'm facing, especially in the last seven, eight months, not winning any tournament, which hasn't happened in many years," said Djokovic, who actually won in Doha in January but may have been referring to grand slams.

"All the top players have been through that. So I guess you've got to go through it, try to learn your lessons and figure out the way, how to get out of it stronger.

"It's a big challenge, but I'm up for it."

Thiem landed in the semifinals for the second straight year -- Djokovic downed him 12 months ago -- and will no doubt face a tougher test in Nadal, who will certainly be well rested.

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Nadal, Thiem and Wawrinka all have yet to relinquish a set.

Nadal and Thiem have locked horns three times on the clay already since April, Nadal winning twice.

"So far I have always played a way worse match the following day if I beat a top guy, so I hope I can improve that," Thiem told reporters.

"It's a joke how tough it is to win a slam, because obviously now I beat Novak. On Friday (I play) Nadal. In the finals there is another top star."

Nadal spent only 51 minutes on court against fellow Spaniard Carreno Busta before an abdominal injury forced the world No. 21 to call it quits.

Early end for Carreno Busta

Appearing in his first grand slam quarterfinal, Carreno Busta -- having the best season of his career -- took a medical timeout and had to leave Philippe Chatrier court.

He returned with tape to his abdominal area and retired after yelling out in pain while hitting a smash.

Rafa on PCB:"Obviously wasn't the perfect way to win, especially vs a friend. Tough when these things happen but he had a great event" #RG17 pic.twitter.com/rrhBKQBkDq — Roland-Garros (@rolandgarros) June 7, 2017

Nadal -- bidding to become the first player in the Open Era to win the same major 10 times -- and Carreno Busta hugged before the 14-time grand slam winner applauded his crestfallen friend off court.

Perhaps Carreno Busta's nearly four-and-a-half hour win over 2016 Wimbledon finalist Milos Raonic in the fourth round took a toll.

It was the third high-profile retirement of the event, following a knee injury to Nicolas Almagro and ankle injury to David Goffin.

In five matches at Roland Garros, Nadal has only spent eight hours on court.

He wasn't worried about breezing through to the last four without being tested, ahead of such a big match against Thiem.

Playing 'very well'

"The past few months, I have been playing very well," said Nadal. "I have played good matches on the whole. I am in the semifinals.

"Maybe I could have had a more difficult match. It wasn't the case.

"But all of the tournament I have played well and despite the weather conditions, I played well. I'm not quite sure that I need a sort of reference match."

Similar to Djokovic, Murray entered the French Open in, for him, poor form. But after struggling in his first two matches, he has clearly raised his level.

The turning point against Nishikori -- who upset Murray at last year's US Open -- came when the latter won the third-set tiebreak without dropping a point.

Making matters worse for Nishikori, he was broken immediately after breaking Murray to begin the fourth.

Wawrinka's lone worrying moment resulted when he almost turned an ankle near the net in the last game against Cilic. He fell to the court but appeared to be okay.