Fourth seed Caroline Wozniacki spurned four match points as she crashed out of the US Open second round in a final-set tie-break against Petra Cetkovska.
Wozniacki, who was runner-up at Flushing Meadows in 2009 and 2014, appeared to have the match in her grasp after she came from a set and 4-1 down to lead 6-5 in the decider.
Cetkovska, however, saved four match points on her serve and then blew her opponent away in the tie-break to win 6-4 5-7 7-6 (7/1) in a thrilling final night match in Arthur Ashe stadium. Wozniacki's shock exit means only three of the top 10 seeds remain in the women's third round.
"It really sucks to lose a match like that," Wozniacki said.
"Here, not playing my best level, but still being so close, and still having my chances but not closing it out, that hurts. That really hurts."
Cetkovska, ranked 149th in the world, has never been past the fourth round of a major tournament and has endured a serious hip injury, for which she had an operation in September last year.
Returning to action in March, the Czech lost in the first round at both the French Open and Wimbledon, before entering the US Open with a protected ranking, which is available to players after long-term injury
"It was sensational," Cetkovska said of her surprise win. "This injury that I've overcome, it was really difficult. Those first months it was extremely difficult.
"Every day I was asking myself if I will be able to play tennis again, to play on such a big stadium, to play such a big match and win it.
"No, to be honest, I was not really thinking of it because it was not really going so well in the beginning.
"So for me it is just an amazing feeling, like satisfaction for everything that I have gone through."
Cetkovska will now face Italy's Flavia Pennetta, who witnessed a drone interrupt her victory over Monica Niculescu in Louis Armstrong stadium.
The flying object flew over the court and crashed into a section of empty seats as play had to be temporarily suspended while security examined the device.
A USTA statement read: "No spectators were in the immediate area of the crash and there were no injuries. "The NYPD responded and is conducting an ongoing investigatio
n." Pennetta admitted she had been unnerved by the drone's arrival. "I was a little bit scared, I have to say," Pennetta said. "With all the things that happen now in the world, I'm imagining, 'Okay, it's a bomb.' That was my first reaction. I think it's normal to think something like that.
"I was trying to keep playing. I saw the police there watching and everything."
Ninth seed Garbine Muguruza is out after the Wimbledon finalist was beaten 7-6 (7/4) 6-7 (4/7) 6-2 by Britain's world number 97 Johanna Konta.
Victoria Azarenka is safely through, however, after she knocked out Belgian Yanina Wickmayer, and the number 20 seed will now face Angelique Kerber, who beat Karin Knapp in straight sets.
Azarenka is due to meet second seed Simona Halep in the quarter-finals and the Romanian also progressed after a comfortable win over Ukraine's Kateryna Bondarenko.
Halep's victory was not unexpected but the world number two has been turning heads off the court, after she rode the tournament bus to Flushing Meadows rather than her own private transport.
Sitting with journalists, coaches and tournament staff, Halep had a simple explanation for her choice of travel: "Because I prefer (the) bus."