World number one Simona Halep christened the newly renovated Louis Armstrong Stadium with a shock 6-2 6-4 loss to unseeded Estonian Kaia Kanepi, becoming the first top seed to lose an opening match at Flushing Meadows.
It was the second consecutive year the Romanian French Open champion exited in the US Open first round.
On a hot and humid day, Halep failed to sustain any kind of service rhythm and her usually stout defence proved no match for the powerful Kanepi's bruising groundstrokes and deft drop shots.
"I have always loved being in New York," said the 33-year-old Kanepi, twice a quarterfinalist at the tournament who has been ranked as high as world number 15.
"I like the atmosphere. I like being here. I love the courts and the climate, and I think that the courts suit my game really well."
Kanepi, world number 44, earned the first break when she launched a back-hand lob over Halep's head to jump out to a 2-1 lead and went on to win five of the first six games while winning 80% of her first serve points in the set.
Frustration for Halep boiled over in the second game of the second set when she smashed her racket on the court, earning a racket abuse warning from the chair umpire.
Halep recovered and it appeared a comeback was on when she broke Kanepi to love to level the second set at 4-4.
But Kanepi completed the upset when Halep sent a service return long on match point.
"Today I just lost," Halep said.
"I didn't play great, but she played really well. I knew that she can play well here. She played quarterfinals last year.
"I didn't find the balance today. I couldn't play better, so that's it."
It was the sixth time in the Open era that the number one seed has lost in the first round of a Grand Slam tournament and the first at the US Open.
Halep had looked primed for a long run in New York after she won the Rogers Cup this month and narrowly missed out on back-to-back titles after losing to Kiki Bertens in the Cincinnati final. She pulled out of last week's Connecticut Open with an Achilles injury.
The Romanian can take small consolation from the fact she has amassed enough ranking points to remain world number one after the two-week tournament ends.
Wawrinka upsets, Murray through
Swiss wildcard Stan Wawrinka conjured up some of his old US Open magic, sweeping past eighth seeded Bulgarian Grigor Dimitrov 6-3 6-2 7-5 at Arthur Ashe Stadium with an upset victory on Monday.
After winning the US Open in 2016 Wawrinka was unable to defend his title last year following two surgeries on his left knee.
But the Swiss, 101st in the world rankings, looked right at home as he opened his account with a ruthless performance against one of the title contenders.
It marked the second consecutive Grand Slam that Wawrinka had drawn Dimitrov, the 33-year-old Swiss rallying from a set down in an opening round meeting at Wimbledon to snap a four match losing run to the Bulgarian.
Meanwhile, Briton Andy Murray beat Australia's James Duckworth 6-7(5) 6-3 7-5 6-3 in a fiery match marked by long rallies in sweltering heat.
It was Murray's first appearance in a Grand Slam since last year's Wimbledon quarter-finals, nearly a year since he underwent hip surgery.
