She was broken four times by Osaka, who looked far more assured throughout as she coasted into her first Grand Slam quarter-final in four years.
“I’m a little sensitive and I don’t want to cry,” said Osaka, who also beat a 15-year-old Gauff at the US Open in their first meeting in 2019.
“I had so much fun out here. This is my favourite court in the world and it means so much to me to be back here.”
Osaka’s current US Open campaign is her best performance in a Grand Slam singles tournament since she returned to tennis last year following the birth of her daughter in 2023.
Osaka conceded just two points off her serve in the entire opening set, which she took with her second break of Gauff, who double-faulted on set point.
The second set was a similar story, with Osaka giving up only four points on serve while pressuring Gauff relentlessly.
Osaka edged clear after breaking Gauff to go 4-2 up and then broke the American again to complete victory.
Osaka will face either Czech 11th seed Karolina Muchova or Ukrainian 27th seed Marta Kostyuk in the quarter-finals.
Kiwi advances to doubles quarter-finals
Erin Routliffe and Canadian partner Gabriela Dabrowski are through to the quarter-finals after a straight-sets win over 13th seeds Cristina Bucsa and Nicole Melichar-Martinez.
The number three seeds won 6-4, 6-2 to book a spot in the final eight.
The pair, who won the title in 2023, have dropped just one set in the tournament so far.