LONDON -- Garbine Muguruza's first major tournament as a reigning Grand Slam champion didn't last long.
Less than a month after winning the French Open, the second-seeded Spaniard was beaten in the second round of Wimbledon on Thursday by a Slovakian qualifier ranked No. 124.
In the biggest upset of the tournament so far, Jana Cepelova beat a listless Muguruza 6-3, 6-2 on Court 1 in less than an hour to reach the third round at the All England Club.
Muguruza was not as sharp Thursday as she was in this tournament last year, when she lost to Serena Williams in the final, or as she was in beating Williams in the final at Roland Garros this month for her first major championship.
"My energy was missing a little today,'' Muguruza said. "From yesterday I felt a little bit tired. During the match and after the match, I'm like, 'Tough day today, empty today.'''
She sprayed ugly shots all over the court Thursday and finished with 22 unforced errors compared to just nine winners. Cepelova had a first-serve percentage of just more than 40 percent but still outplayed Muguruza with 14 winners and 12 errors.
"She played great, no fear, trying a lot of stuff that was working,'' Muguruza said. "But my energy wasn't there. I was trying but it didn't work at all.''
Cepelova, Slovakia's No. 5 female player, had to win three matches in qualifying to make it into the main draw. It's not the first time she has knocked off a top player. Cepelova ousted Simona Halep in the first round at Wimbledon last year, also on Court 1, and beat Williams at a tournament in Charleston in 2014.
"Last year I beat Halep on the same court and I had great memories," the 23-year-old Cepelova said. "I am so happy."
The last time a second-seeded woman lost at Wimbledon before the third round was in 2013, when Victoria Azarenka was beaten in the second round.
Five-time Wimbledon champion Venus Williams won yet another match at the All England Club as three American women picked up victories as the tournament scrambled to get back on schedule.
The eighth-seeded Williams, at 36 the oldest player seeded in the top eight at a major tournament since Martina Navratilova at Wimbledon in 1994, beat Greek qualifier Maria Sakkari 7-5, 4-6, 6-3 to reach the third round.
It turned out to be an unexpectedly close, 2½-hour match between Williams, winner of seven Grand Slam titles and playing in her 19th Wimbledon, and Sakkari, making her first appearance at Wimbledon and third at a major.
Williams, who had 38 winners but 31 unforced errors, won the most recent of her five Wimbledon titles in 2008. Since 2011, she has not been past the fourth round.
Third-seeded Agnieszka Radwanska, the 2012 runner-up at Wimbledon, saved three match points and came back to beat 18-year-old Croatian Ana Konjuh, who accidentally stepped on a tennis ball and injured her right ankle in the next-to-last game.
Radwanska pulled out the 2-6, 6-4, 9-7 victory in the second round after the 103rd-ranked Konjuh was broken while serving for the victory at 5-4 and 6-5 in the third set.
Radwanska has made it to at least the semifinals at Wimbledon in three of the past four years.
Keys, seeded No. 9 after breaking into the top 10 for the first time this month, reached the third round with a 6-4, 4-6, 6-3 win over Kirsten Flipkens. Keys, a quarterfinalist last year, had 48 winners -- more than double the Belgian player's 22.
No. 18 Stephens, who reached the quarterfinals here in 2013, defeated China's Peng Shuai 7-6 (5), 6-2 in a first-round match that was delayed.
Other women's winners included fourth-seeded Angelique Kerber advancing with a 6-1, 6-4 win over Varvara Lepchenko and No. 5 Simona Halep, who beat Francesca Schiavone 6-1, 6-1. No. 14 Samantha Stosur was knocked out 6-4, 6-2 by 2013 runner-up Sabine Lisicki.
No. 11 Timea Bacsinszky beat Luksika Kumkhum 6-4, 6-2, Annika Beck ousted Britain's Heather Watson 3-6, 6-0, 12-10, and France's Kristina Mladenovic, seeded No. 31, was eliminated 6-3, 6-3 by Aliaksandra Sasnovich.