Pegula needed just 56 minutes to get past Kenin, the former Australian Open champion now ranked 110th, dropping just seven points on serve.
"I was just trying to stay focused on what I needed to do," said Pegula, who is among a trio of players who could supplant Aryna Sabalenka atop the world rankings in New York.
Pegula, who reached the US Open final in 2024, next meets another former finalist, Leylah Fernandez. The Canadian breezed past Thailand's Mananchaya Sawangkaew 6-4, 6-1.

Medvedev, who has struggled in the hard court build-up to the year's final Grand Slam, dominated 731st-ranked Gorzny.
He fired 14 aces and saved the lone break point he faced, although he was distracted briefly when a pair of small birds perched on the Louis Armstrong Stadium net and he was forced to replay a point he thought he'd won.
"I saw them straight away, and I thought the point would stop straight away, and we didn't," Medvedev said. "And the moment I hit the winner, we stop. I was not happy with the decision."
He was happy enough with his game, however.
"The first two sets he was not playing the best tennis of his life maybe. The third set was much more competitive," Medvedev said.
"At the same time I feel like I had more break points and put more pressure on him."
US Open 2026
The US Open is the fourth and final Grand Slam of the tennis season, running from August 30th to September 13th. It is a hard-court tournament held at Flushing Meadows in New York City. Follow the links below for more information!
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