Stuttgart - Three-time defending Stuttgart champion Maria Sharapova lost her opening claycourt match of the season Thursday, going down 2-6, 7-5, 6-1 to Germany's Angelique Kerber in the German city.
The defeat was Sharapova's first at the venue after sweeping to the title in 2012, 2013 and 2014 on the back of 13 successive wins.
It also means the French Open champion will lose her world number two ranking to Simona Halep next week.
The defeat for 28-year-old Sharapova ended a seven-year streak of 64 successive wins on clay after securing the first set.
Kerber, the world number 14, will face Sharapova's Russian compatriot Ekaterina Makarova in the quarter-finals.
Sharapova, who skipped Russia's Fed Cup semi-final win over Germany with a leg injury last weekend, was on course for a comfortable win at one stage, leading by a set and 5-4.
But left-handed Kerber won three games in a row to sneak the second set 7-5 before eventually taking victory after two hours and 27 minutes.
Sharapova finished with 44 winners to 40 unforced errors while Kerber was 22-20.
World number four Petra Kvitova also suffered a shock defeat, beaten in straight sets by unseeded American Madison Brengle.
Brengle, 25, ran out a 6-3, 7-6 (7/2) winner as Kvitova failed to make it past the second round in her first tournament since February.
Brengle broke the 2014 Wimbledon champion's serve seven times to clinch victory in just over 90 minutes.
Kvitova, who took a six-week break to recover from exhaustion, resumed training three weeks ago and won both her Fed Cup semi-final singles rubbers as the Czechs beat France 3-1 last weekend.
The unseeded American, who reached the last 16 at the Australian Open, will next face France's Caroline Garcia who put out Carina Witthoeft of Germany 7-6 (7/4), 6-2.
"I think that Madison played a solid match. She didn't miss much and it was really difficult for me because when I had the opportunity for winners I missed," said Kvitova, who hit 39 unforced errors and the same number of winners.
"The confidence wasn't really high then and I didn't feel physically there as well.
"I mean I was still tired probably from the Fed Cup. And on the clay you need to be physically ready for it. So, that was one of the reasons as well. I need to be still patient and I'm looking forward to next week which I'm going to use to practice on clay."
Fourth seed Caroline Wozniacki defeated Czech veteran Lucie Safarova 7-6 (7/5), 6-1 in her first outing on clay this year.
The Dane won just one claycourt match in 2014 but with the French Open fast approaching she has enlisted the help of three-time Roland Garros champion Arantxa Sanchez-Vicario to be part of her coaching team this season.
Wozniacki next plays either Belinda Bencic or Carla Suarez Navarro.