NEW YORK – Top-seeded Ana Ivanovic lost in one of the biggest upsets in tennis history Thursday, stunned by 188th-ranked Julie Coin 6-3, 4-6, 6-3 in the second round of the U.S. Open.

Coin screamed when Ivanovic’s last shot sailed out, then hopped for joy and hit an extra ball high into the stands. Ivanovic quickly gathered her gear and left the court, her hopes of another Grand Slam championship dashed.

Even after Ivanovic struggled in the first round while coming back from an injured thumb, there was no way to see this coming.

Coin spent much of the year playing in minor league events, and nearly got knocked out of a qualifying event to merely make it into the Open.

It just didn’t add up, even to the 25-year-old Frenchwoman with a mathematics degree from Clemson.

Asked whether she’d thought such a win was possible, Coin gave a simple answer.

“No,” she said.

And when did she believe it might happen?

“I guess when it was over,” she said, drawing a huge ovation from the crowd at Arthur Ashe Stadium.

If there was any suspicion that Coin was wavering, she steadied herself by winning 10 straight points in the third set. It was Ivanovic who looked jittery, hitting shots directly into the net or way out.

Never before in the Open era that began in 1968 had the No. 1 woman lost this early in the tournament.

During the first four days at the U.S. Open, almost of the favorites had won. Handily, too, with Venus Williams leading the romps earlier in the day.

But when the Ivanovic-Coin match was moved from the smaller Louis Armstrong Stadium to the main Ashe stage, fans hardly knew what was in store.

Tentative at times, Ivanovic seemed to regain her edge midway through third set. The French Open champ led 40-0 in the fifth game and was about to break Coin’s serve when suddenly the momentum shifted.

Coin came back to hold, starting her decisive streak.

Ivanovic tried to stave off Coin in the final game, but it was too late for the 20-year-old Serbian star. Coin won on her third match point – quite a result for someone playing in her first tour-level event.

Coin had tried to qualify for the Australian Open, French Open and Wimbledon and never made any of them. And she certainly wasn’t anything bankable going into this match – she’d earned less than $100,000 lifetime as a pro, and was facing someone who’d won nearly $6 million.

Next up for Coin in the third round is No. 32 Amelie Mauresmo, who beat Kaia Kanepi 2-6, 6-4, 6-0. Coin and Mauresmo once played at the same club near Paris and shared the same coach, though they don’t know each other well.

“I know she was No. 1,” Coin said.

Going into this Open, Ivanovic had played only two matches since Wimbledon while her thumb healed. The injury forced her to withdraw from the Olympics before they began, limited her practice time and sent her from Beijing to Australia for treatment.

Pain-free, she made no excuses after escaping against No. 57 Vera Dushevin in the first round.

Top-seeded Rafael Nadal and Serena Williams were scheduled to play night matches.

James Blake, David Ferrer, Andy Murray and Dinara Safina joined Venus Williams in moving into the third round at Flushing Meadows.

The seventh-seeded Williams overwhelmed Rossana de Los Rios 6-0, 6-3, winning on her fifth match point and needing only 59 minutes to advance.

“I’m very satisfied so far, the way it’s gone,” Williams said.

Williams breezed past an opponent ranked 117th. After teaming with her sister to win Olympic gold in doubles, she stayed on course to play Serena in the quarterfinals here.

“Whichever way the draw goes, whichever way the matches go, as long as hopefully it’s a win for me, I’m pretty happy about it,” she said.