Charleston - World number one Serena Williams crashed out of the WTA Tour's Family Circle Cup on Tuesday, losing her opening match in straight sets to world number 78 Jana Cepelova.
The 20-year-old Slovakian Cepelova defeated defending champion Williams 6-4, 6-4 in a second-round match at the claycourt tournament.
Williams, who won this event in 2013, 2012 and 2008, also had her 15-match tour win streak snapped.
Williams was fresh off winning her sixth Miami title and 59th singles crown by beating world No 2 Li Na, of China, on Sunday. She also won in Brisbane earlier this year.
Unseeded Cepelova, who appears to be headed for a breakout year, was facing 17-time Grand Slam winner Williams for the first time. Cepelova won 55 percent of her first serves and 71 of 136 total points in the 84-minute match.
She advances to face Elena Vesnina of Russia, who beat another Slovakian, Anna Schmiedlova, 6-2, 6-1.
Williams, 32, blasted four aces but committed three double faults. She won just 12 of 28 points on her second serve against the fifth-ranked female player from Slovakia.
Cepelova's first career win over a top-10 player comes against the number one player in the world. Her previous biggest win was beating former Charleston champ Samantha Stosur earlier this year in Doha. Stosur, of Australia, was ranked 16th in the world.
Her best tournament result was making the quarter-finals in Shenzhen, China earlier this year.
Cepelova, who will turn 21 next month, beat American wildcard Melanie Oudin 7-6 (7/2), 6-2 in the first round.
Serena's sister Venus was an opening-round winner on Tuesday.
The 11th-seeded Venus held off Czech Barbora Zahlavova Strycova 6-3, 0-6, 7-5 in two hours, 18 minutes. Venus hasn't won this event in a decade.
Seventh-seeded Stosur, the 2010 Charleston champ, got past Kazakhstan's Yaroslava Shvedova 6-3, 5-7, 6-1 in second-round play.