Vavassori and Errani downed 2022 Wimbledon singles winner Elena Rybakina and 2024 US Open singles finalist Taylor Fritz 4-2 4-2, before outlasting Karolina Muchova and Andrey Rublev 4-1 5-4 (7-4) in the quarter-finals.
The pair had added motivation to retain their crown as the year's final major took a new approach to the event beloved by fans but often lost in a schedule that is dominated by singles action, moving the competition to five days before the main draw.
This year's format saw eight pairings based on the combined singles rankings and eight wild cards, a move that left some doubles competitors fuming, including wildcards Vavassori and Errani.
"We're also playing for all the doubles players that could not be here, so we tried to do our best," said Vavassori, after downing Fritz and Rybakina.
There were, however, large crowds on both Arthur Ashe and Louis Armstrong on Tuesday, and they did see some singles stars winning.
The 2022 US Open champion Iga Swiatek showed little sign of fatigue a day after clinching the title in Cincinnati, as she and teammate Casper Ruud beat American duo Madison Keys and Frances Tiafoe 4-1 4-2 in their opener.
They then made easy work of grand slam doubles finalist Caty McNally and partner Lorenzo Musetti winning 4-1 4-2 to claim another of the semi-final spots.
The semis and final are set for Wednesday.
"Last two days felt like one long day but I'm super happy to be here and playing with Casper," said Swiatek. "Didn't have time to play many doubles to practise but I think I can improvise pretty well."
Cincinnati men's winner was also in action, Carlos Alcaraz partnering Emma Raducanu against No.1 seeds Jack Draper and Jessica Pegula.
But "Raducaraz" lost 4-2 4-2, eliminating the only pairing featuring two singles grand slam champions from the draw.
US duo Taylor Townsend, the women's doubles No.1, and Ben Shelton beat fourth seeds Amanda Anisimova and Holger Rune 4-2 5-4 (7-2).
The revamped event's star power was dented by the last-minute withdrawal of Italian Jannik Sinner, a day after illness forced the world No.1 to retire five games into his Cincinnati final with Alcaraz.
Americans Danielle Collins and Christian Harrison replaced Sinner and partner Katerina Siniakova.
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