Keys crashed out of the first round at Cincinnati last month but appeared right at home on the New York hard courts, where she was runner-up in 2017, as she overwhelmed her opponent with 21 winners.
Pegula beat the 17th-seeded Keys in their only previous meeting last year and was considered one of the U.S.’s brightest hopes after winning the Montreal title last month.
However, on Monday she lacked her usual firepower and finesse.
“I’ve had so many amazing moments in New York,” said Keys, who is playing in her 12th US Open main draw.
“Being able to at any moment come back from any difficult positions I’ve been in matches has been amazing.”
Keys broke her opponent’s serve with a backhand winner in the second game of the first set and broke Pegula again on the fourth try in game six.
Pegula was clearly off her game and threw her racquet down in frustration as she helped Keys to the break with a double fault and a backhand error in the fifth game of the second set.
Pegula broke back immediately in the sixth game but Keys kept her cool, retaking the lead as she broke her opponent’s serve in the seventh game.
Keys, who counts Pegula as a close friend, pumped her fist in a subdued celebration as the top-ranked American dropped her serve again when she sent a forehand shot into the net on match point.
“It’s always tough having to play a friend… when we get on the court it’s all business,” Keys said in a courtside interview.
Zheng becomes the first Chinese player to reach the quarterfinals of the US Open since Wang Qiang in 2019. She did it by overpowering the fifth-seeded Tunisian with an aggressive baseline game that produced 21 winners.
“I feel just super happy and excited to play in a big stadium and have a really good performance today,” the 20-year-old Zheng told the Louis Armstrong Stadium crowd.
For the fifth-seeded Jabeur, who committed 33 unforced errors and has appeared ill at times during her US Open run, it was a disappointing finish after reaching the finals of three of the last five Grand Slam events, including the last two Wimbledons.
Zheng’s win mean three of last year’s four US Open singles finalists are gone, leaving only second-seeded Aryna Sabalenka, a Belarussian who will take over the No. 1 spot in the WTA rankings because of the fourth-round loss by No. 1 seed Iga Swiatek.
Zheng will play the winner of the match later between Sabalenka and No. 13 Daria Kasatkina. That will give Zheng the chance to play for more history – to equal the best runs ever by Chinese players at the US Open, semifinals appearances by Peng Shuai in 2014 and Li Na in 2013.
The Associated Press and Reuters contributed to this story.