The seven-times Grand Slam champion was humbled 6-1 6-2 by her younger sister in their 30th career meeting and said it was the best she had seen Serena play against her.
"She played untouchable tennis," Venus said after the 72-minute match, during which the 17th seed Serena fired down 10 aces.
Winning the tournament would add a 24th Grand Slam singles title to Serena's name to tie the record of Australian Margaret Court.
"Whoever she plays, she's going to earn it," Venus said. "It's not like people don't try. People will try against her."
The evening match at Arthur Ashe Stadium saw Venus succumb to her equal worst defeat at the hands of her sister.
Serena next faces Estonia's Kaia Kanepi, who ousted top seed Simona Halep in the first round.
"Obviously I hope she doesn't play that well against me every time because I don't think anyone has a chance," Venus added.
(Reporting By Amy Tennery, Editing by Nick Mulvenney)
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