After enjoying her maiden overseas grand slam victory, Preston's Open adventure ended abruptly on day four with 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).
Kasatkina offered much stiffer resistance but eventually succumbed 6-1 6-4 to one-time world No.2 Paula Badosa on the ninth match point of an epic encounter that stretched over two days.
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.
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.
The Australian No.1 also conjured two break point chances to level up at 5-5 before Badosa finally closed out the contest to book a second-round date with fourth seed Coco Gauff.
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.
"OK, at some point you just know that she's nervous because when you cannot win one match, then two, three, four, it gets into your head," Kasatkina said.
"Crazy stuff. I was trying to build a point and then see how the situation is going to end up.
"That was a fun two days, to be honest."
Keenly watched on by Tennis Australia's new CEO, former NRL chief Andrew Abdo, Birrell also put up a great fight before bowing out in three sets to Russian 18th seed Ekaterina Alexandrova.
Like Preston, the 28-year-old was playing her first US Open second-round match.
But after a nervy start, Birrell snared the second set before falling 6-1 2-6 6-3.
Despite their exits, Birrell and Preston will both depart New York with new career-high rankings - and well-earned $US190,000 ($A265,000) pay cheques.
Unless Joint goes deep in the draw, Birrell will be Australia's new national No.1 at 55th in the world rankings, while Preston is slated to climb to No.91.
Joint takes on ninth seed Elina Svitolina later on day four, hoping to reach the third round in New York for a third straight year.
Men's sixth seed and three-time Open quarter-finalist Alex de Minaur finally launched his title bid with an impressive 6-2 6-2 6-4 win over Italian qualifier Andrea Guerrieri.
This AAP article was made possible by support from Tennis Australia.
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