Gauff clawed back from 5-3 down in the second set to reach the third round and claim her second consecutive win on the world's largest stage for tennis, the 23,771-capacity crown jewel of Flushing Meadows.
Gauff was viewed as a possible heir apparent to the Williams sisters when as a 15-year-old she stunned Venus in the first round of Wimbledon in 2019. Her best result at a Grand Slam so far was reaching the French Open final in June.
"It's a really big court and I've been watching Venus here, Serena here and now I'm playing here," Gauff said in an on-court interview.
"It's an honour to open up the court for her tonight."
Next up for the 12th seeded Gauff is a meeting with hard-hitting fellow American Madison Keys (27) after she won a tense third-set tiebreaker to see off Italy's Camila Giorgi (30) 6-4 5-7 7-6(6).
The loss is sure to sting for Giorgi, who served for the match while leading 5-2 in the third set but could not close it out and committed a flurry of errors in the tiebreak.
Giorgi converted just four of her 16 break point opportunities while 20th seed Keys struck eight aces and 30 winners at Louis Armstrong Stadium.
"I was just telling myself to keep my legs moving, swing at the ball and not overthink things," Keys said.
"Just rely on my athleticism and luckily I got this win."