New York: Garbine Muguruza has lost in the second round in back-to-back majors since winning the French Open title.

The third-seeded Spaniard was upset in straight sets Wednesday by Anastasija Sevastova, who returned to tennis last season after a nearly two-year retirement. The 48th-ranked Sevastova won 7-5, 6-4 to reach the third round at the U.S. Open for the first time.

 Garbine Muguruza, of Spain, watches the video board after a call was challenged during her match against Anastasija Sevastova, of Latvia, at the U.S. Open tennis tournament. (AP)

Muguruza has never been past the second round at Flushing Meadows. The 22-year-old fell to 124th-ranked Jana Cepelova in the second round at Wimbledon after she beat Serena Williams in the French Open final for her first major title.

She needed three sets to win her first-round match Monday, when she struggled with her breathing. Down two breaks in the second set Wednesday, she saved two match points and rallied to get the set back on serve. Then she got broken to end the match.

 Anastasija Sevastova, of Latvia, reacts after a point against Garbine Muguruza, of Spain, during the U.S. Open tennis tournament. (AP)

The 26-year-old Sevastova, who reached the round of 16 at the 2011 Australian Open, retired in May 2013 because of a series of injuries, mostly to her back. She returned in January 2015.

She had been 0-2 against top-five opponents.

Sevastova said moments like her upset of Muguruza are why she came out of retirement.

In an on-court interview, the 26-year-old Latvian said she returned to tennis early last season for "Grand Slams, playing on the biggest stage."

 Anastasija Sevastova, of Latvia, left, clasps hands with Garbine Muguruza, of Spain, after Sevastova won their match 7-5, 6-4, during the U.S. Open tennis tournament. (AP)

Sevastova stepped away for nearly two years because of a series of injuries, mostly to her back. She says: "It's amazing — on Ashe, in night match. What's going to be bigger?"

Up two breaks in the second set, Sevastova was serving for victory and had two match points. But Muguruza got both breaks back to put the pressure on. Sevastova then broke the third-seeded Spaniard's serve to clinch the win. She acknowledged she was shaking at the end, adding: "I had to solve my head, my self, all the thoughts of what could be, what could not."