The first Australian through to round two was the first to exit following a 6-1 6-1 loss to big-hitting American Taylor Townsend.
The 20-year-old wildcard was eliminated in just 48 minutes on Wednesday (Thursday AEST).
Preston was one of five Australians scheduled for day-four action at Flushing Meadows.
Australian women's No.1 Daria Kasatkina was also removed from the draw, but not before offering more considerable resistance against Spaniard Paula Badosa.
The pair resumed their stop-start affair that was halted on Wednesday night in sensational fashion.
After first being forced off court because of rain early in the second set, while trailing Badosa 6-1 1-2, Kasatkina was delighted when officials called it a night immediately after she saved a third match point.
Badosa was furious and had to return 15 hours later trying to serve out the contest at 5-4 and deuce in the second set.
Kasatkina saved her first two match points in an epic 22-point game serving at 3-5 in the second set, before fighting off another six more.
Kasatkina also conjured two break point chances to level up at 5-5 before Badosa, a one-time world No.2, finally closed out the contest to book a second-round date with 2023 champion Coco Gauff.
Maya Joint takes on ninth seed Elina Svitolina, hoping to reach the third round in New York for a third straight year.
Kim Birrell is up against Russian Ekaterina Alexandrova believing she can also topple the Russian 18th seed after taking down world No.5 and 2024 US Open finalist Jessica Pegula at the French Open.
And men's sixth seed and three-time Open quarter-finalist Alex de Minaur will finally launch his title bid after his first-round stoush with Italian qualifier Andrea Guerrieri was postponed on Wednesday night because of rain.
The delay has left de Minaur facing a brutal schedule, needing to win seven best-of-five-set encounters in 12 days to land a maiden grand slam title.
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