Petra Kvitova became the first reigning Wimbledon champion to lose in the first round of the US Open in the Open era last night.
Third seed Maria Sharapova was given a stern test by British teenager Heather Watson before coming through in three sets.
Czech fifth seed Kvitova has had a difficult time since beating Sharapova in the final at the All England Club in July, winning only two matches, and she looked shaky from the start against Alexandra Dulgheru of Romania at Flushing Meadows.
In contrast, world number 49 Dulgheru played a very solid match and, after breaking Kvitova to lead 5-3 in the second set, she served out a 7-6 (7/3) 6-3 victory to love.
Sharapova, meanwhile, fought back from a set and a break down to defeat gutsy Watson 3-6 7-5 6-3 in a match that lasted two hours and 34 minutes on Arthur Ashe Stadium.
After holding her nerve to serve out the opening set, 19-year-old Watson battled back from 4-1 down in the second set and then recovered from 3-0 in the decider, but it was not to be.
Sharapova was effusive in her praise of Watson and rated the contest as one of her hardest first-round clashes.
The Russian said: "No doubt that it was one of the toughest that I've had. To be honest, it's quite unexpected, obviously not really knowing too much about my opponent and not facing her before.
"She just came out and played really smart. There's no doubt that I wasn't playing my best tennis. She was smart in making me hit another ball. I was making so many errors out there. She stuck to her gameplan. She kept grinding."
The victory took Sharapova's record in three-set matches this year to 12-0, a statistic she put down to having complete faith in her battling qualities.
"I think it's just a matter of belief, whether I haven't won three-set matches here or whether I have a great record," said the world number four.
"I think it's just a matter of belief within myself that no matter how well or badly I'm playing or my opponent is playing, I know I can tough it out."
It was Watson's first appearance in the main draw at the US Open, two years after she won the junior title, and she relished the opportunity to play on tennis' biggest court.
She said: "I had a lot of fun today. It's what I want to do. I want to be out there on the big courts playing the top players. It was a really great match, very competitive. We played some really great tennis.
"I had my chances in the second set. You have to create the opportunity but also execute, and I was probably a bit too defensive on those important points.
"But I always believed I could win. There's no point in my going out there if I don't believe that I can win.
"I just wanted to make every ball, make her play every ball, and just fight. Because Maria's a fighter. She's never going to give up. That's what makes her a champion. That's why she's won this tournament before."
Second seed Vera Zvonareva avoided Sharapova's drama as she eased past qualifier Stephanie Foretz Gacon of France 6-3 6-0.
Despite being a two-time grand slam finalist, including last year at Flushing Meadows, the Russian does not attract the attention of her fellow seeds.
Zvonareva, though, insists that does not bother her in the slightest, and she said: "That's probably the last thought on my mind.
"I want to go out there and play deep into the tournament because it is a grand slam, because it is prestigious, because we've got the best field in the world here."
Eighth seed Marion Bartoli was tested by Russia's Alexandra Panova before prevailing 7-5 6-3 while in the battle of the Polish Radwanska sisters, 12th seed Agnieszka won her third meeting with Urszula 6-2 6-3 to take a 2-1 lead in their head-to-head series.
There were also victories for seeds Julia Goerges, Lucie Safarova, Peng Shuai, Anabel Medina Garrigues, Maria Kirilenko, Nadia Petrova and Dominika Cibulkova.
Ninth seed Samantha Stosur was in impressive form out on Court 11, the Australian defeating Sweden's Sofia Arvidsson 6-2 6-3 to ease into round two.