After three days of the top players winning decisively, fifth-seeded Tsonga was upset by Martin Klizan of Slovakia in the second round in the first shock of this year's Open.
The 52nd-ranked Klizan won 6-4, 1-6, 6-1, 6-3.
Roddick, on his 30th birthday, announced this tournament will be his last, saying he no longer felt the drive to compete at the highest level and didn't want his career to peter out.
"I don't know that I'm healthy enough or committed enough to go another year," Roddick said. "I've always wanted to, in a perfect world, finish at this event. I have a lot of family and friends here. I've thought all year that I would know when I got to this tournament. When I was playing my first round, I knew."
Roddick, a former No. 1 ranked player, is currently No. 20 in the world. He has one Grand Slam victory, the US Open in 2003. He played in four Grand Slam finals, losing to Roger Federer in each.
"I've had some great battles with him for a long, long time," Federer said. "The Wimbledon finals come to mind, the ones we played together. He's a great, great competitor and a great champion, really."
"He told me a while ago — last year — that this would be it," she said. "We were talking about it. I was just thinking, 'Change your mind, Andy. Change your mind.' But I guess he didn't."
Kim Clijsters also says that the US Open will be her last professional tennis tournament. She lossed her singles match Wednesday, and has only the doubles competition left before her retirement. She won four Grand Slam titles.
"It's been an incredible journey," Clijsters said, "and a lot of dreams for me have come true because of tennis."
Venus Williams came within two points of winning Thursday, but dropped five of the last six games and ended up exiting early at a tournament she's won twice, beaten 6-2, 5-7, 7-5 by sixth-seeded Angelique Kerber of Germany in a nearly 3-hour match.
Asked after the match if she's ready to join Andy Roddick in retirement, Williams replied: "No, because if I could have made two more shots, I probably could have won that match. There's a big difference for me because I'm beating myself. I'm not getting destroyed out there. ... If I was out there and people were killing me, maybe it's time to hang it up."
Before Tsonga's loss, top-five seeds on the men's and women's sides had played 14 matches — and won all 14 in straight sets.
Tsonga was the runner-up at the 2008 Australian Open and a semifinalist at Wimbledon this year. He had reached at least the third round in 18 straight Grand Slam trips.
"Today I was not in a good shape," he said. "I didn't play good tennis. It seemed like I couldn't hit the ball enough hard to put my opponent out of position. I don't really know why it was like this today, but sometimes it's happen with me."
The 23-year-old Klizan, meanwhile, had failed to make it past the second round in three previous Grand Slam appearances. He had never defeated an opponent ranked better than No. 49.
"I had no pressure," Klizan said. "If I lose, then I lose. I lose with (a) good player. But I won and I'm very happy. It means for me more that I beat finally a guy from top 10."
This year's Open has generated plenty of drama in one area: comebacks from two sets down. American Mardy Fish rallied to beat Nikolay Davydenko 4-6, 6-7 (4), 6-2, 6-1, 6-2, the 10th time in this tournament a man has won after losing the first two sets — already an Open record.
The 30-year-old Fish, seeded 23rd, missed two months this season because of an accelerated heartbeat but showed few signs of fatigue in playing nearly 3 1/2 hours.
Davydenko had an interesting take on the match, suggesting men should only play best-of-three sets, rather than five.
"Why (do) girls play best of three sets and we should play best of five sets and have the same prize money?" Davydenko said, reviving a familiar debate.
"Why are we playing five-set matches? We need to play best of three in Grand Slams. Everybody will support (that idea, even Roger) Federer. For Federer, it's easy to win in one hour, two sets. No need to run (for) a third set," Davydenko said.
And after Tsonga lost, another top-five seed was at least pushed beyond a straight-sets finish. Second-seeded Agnieszka Radwanska was down a set and a break to 39th-ranked Carla Suarez Navarro. Then she won 11 straight games for a 4-6, 6-3, 6-0 victory.
A week before the start of the Open, Ana Ivanovic couldn't walk without pain in her right foot.
"That's when I started to panic a little bit," she said.
Two matches into the tournament, the 2008 French Open champion is feeling healthy — and relaxed. The 12th-seeded Ivanovic and another Serbian former top-ranked player, Jelena Jankovic, have quietly reached the third round at Flushing Meadows. Each has dropped just nine games through a pair straight-set wins.
Asked if the torn tendon is fully healed, Ivanovic laughed and said, "I still have a handful of pills every morning."
Ivanovic has been trying to regain her health and her confidence for the last four years. She has yet to make it back to even a quarterfinal of a Grand Slam event.
"I'm really motivated. I want to get back to the top and back in contention to win Grand Slams again," Ivanovic said. "It's been a long process of getting my mind there and my body and game and everything together. Still, it's going to be a lot of hard work and long process, but I'm starting to enjoy it as well.
"I know if it doesn't happen this week, it's coming."
Kei Nishikori, seeded 17th on the men's side, eliminated American Tim Smyczek.