The gritty Gold Coaster wore down Croatian Petra Marcinko 3-6 7-6 (7-4) 6-3 to finally reach the second round after losing all three of her previous Flushing Meadows openers in 2023, 2024 and 2025.
Young gun Maya Joint and veteran James Duckworth also advanced on a banner day two for the Australian contingent.
Joint rallied to take out higher-ranked Russian Liudmila Samsonova 3-6 6-2 6-2 to continue her revival after a horror start to 2026, while Duckworth notched a mighty 5-7 6-3 6-2 7-6 (10-8) comeback victory over 2026 French Open semi-finalist Matteo Arnaldi, the men's 30th seed.
But a beaming Birrell stole the day in burying her first-round hoodoo after being forced to return to court 7 following a nervy 14-hour rain delay.
"I woke up around 5am, like wide awake, ready to step out on court and my alarm wasn't for a few more hours," she said.
"So I had to calm myself back down, and try to clear my mind and then managed to get back to sleep."
After fending off her match point in the 12th game of the second set on Sunday, the 28-year-old was still trailing by a set and a mini break in the second-set tiebreaker before rallying to post one of the most satisfying wins of her career.
Birrell had lost in straight sets to Marcinko on grass at Eastbourne two months ago, having dropped the opening set 6-0 in their first meeting in February, which Birrell won in Texas.
"That's crazy," Birrell told AAP after earning a guaranteed pay day of $US190,000 ($A265,000) - or more if she topples Russian world No.19 Ekaterina Alexandrova next up.
Birrell and coach Matt Fraser are wedding planning for their upcoming big day in Kingscliff and reckon the massive cheque will go nicely on their honeymoon.
"Oh my gosh, I don't think I'll be spending it here," Birrell said.
"I'll definitely save some of it. We're getting married at the end of the year so that helps a lot and maybe I'll buy some extra flowers.
"And we've got a mortgage. Yeah, the mortgage."
Birrell is also slated to soar 16 spots to a career-high world No.55, displacing Talia Gibson as Australia's new No.1.
Birrell, Joint and Duckworth follow WA rising star Taylah Preston in progressing.
Turning 35 in January, Duckworth has finally reached round two at all four grand slams and next faces China's Yibing Wu for a place in the last 32.
Joint had lost 13 of 14 matches since January before starting to turn her season around during the American hardcourt swing.
Now the 20-year-old has earned a crack at ninth seed Elina Svitolina.
While the quartet marched on, Aleksandar Vukic was unable to win his weather-delayed epic against Rei Sakamoto.
Sakamoto was up a break deep in the deciding set when their battle resumed, and the Japanese youngster quickly won six more points on serve, without dropping any, to close out a 6-4 6-7 (5-7) 6-4 3-6 6-4 victory.
Alexei Popyrin and Rinky Hijikata were both fighting hard to also secure second-round berths on day two.
Popyrin and Hijikata both snatched the second sets against former semi-finalist Grigor Dimitrov and third seed Felix Auger-Aliassime respectively to level up their night matches before rain once again forced the suspension of play.
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