Maria Sharapova dropped the first set but battled back to beat Timea Babos and reach the third round. The big names continue to struggle at Flushing Meadows with Nick Kyrgios, Fabio Fognini and Pablo Cuevas all losing.
Maria Sharapova survived a first set scare to defeat Hungary's Timea Babos 6-7, 6-4, 6-1.
Sharapova, who produced a superb display to beat second seed Simona Halep in the first round, underlined her credentials as a contender at Flushing Meadows with a gritty display after letting the first set slip away on a tie-break.
"It wasn't my best tennis today, it was a bit scrappy, but sometimes that's good because you through and you get another chance," Sharapova said.
The five-time Grand Slam champion, who continues her return from a doping ban, fired 12 aces with 39 winners and 36 unforced errors.
"In the second set I felt physically fresh and that gave me confidence. I knew she had a difficult first match here so I used that as confidence. I wanted to be the fittest player out there at the end, and I felt I was," she added.
Australia's Nick Kyrgios suffered a first round defeat to world number 235 and compatriot John Millman 6-3, 1-6, 6-4, 6-1.
The 14th seed struggled with a shoulder injury sustained in the fourth game of the third set and then berated himself for lacking dedication.
Two weeks after upsetting Rafael Nadal on the way to the biggest final of his career, Kyrgios was due to face Roger Federer in the fourth round.
"Early in the third set I hit one serve and I never felt the same after that," Kyrgios said. "Something didn't feel right in my arm."
"I've had a diabolical year at the Slams," Kyrgios said. "It doesn't surprise me. It's just the story of my career, really. I will have good weeks. I'll have bad weeks. It's just a rollercoaster.
"I'm not having the greatest year like I should have done, but the last three months have been a nightmare, really."
Day of shocks
Bouchard: “It’s one of those matches you kind of want to forget about. I just didn’t really know what to do out there.”
Elsewhere, seeds Fabio Fognini and Pablo Cuevas both suffered suprising defeats.
Fognini was beaten in four sets by fellow Italian and world number 144 Stefano Travaglia, while Cuevas lost in straight sets to Damir Dzumhur of Bosnia.
On the women's side, Eugenie Bouchard once again struggled at a major with a comprehensive straight sets defeat by Evgeniya Rodina, as the Canadian's slide down the rankings continues.
However, Juan Martin del Potro beat Switzerland's Henri Laaksonen in straight sets to progress and women's fourth seed Elina Svitolina beat Katerina Siniakova, despite dropping the second set on a tie-break.