Contesting his second ATP quarter-final in as many weeks, Purcell succumbed 7-6 (7-4) 6-4 to Czech Jiri Lehecka after being unable to convert his only break point of a tense serving shootout.
The defeat was just Purcell's third in his past 13 matches, with the other two coming against world No.1 Carlos Alcaraz in Cincinnati and former top dog Andy Murray in Toronto.
The 25-year-old's reward is another rankings rise to a fresh career-high No.43 when he arrives in New York on Monday for the US Open.
But Purcell will rue in his wretched luck in Friday's Open draw when he was pitted against fellow Sydneysider and good mate Chris O'Connell in the first round.
As if that wasn't bad enough, the winner will almost certainly run into 2021 US Open champion and third seed Daniil Medvedev in round two.
Purcell and the 67th-ranked O'Connell, though, were far from the only Australians to cop unfortunate draws for the year's final grand slam.
A fortnight after reaching his career-best ranking of 48th, Aleksandar Vukic will face former finalist and reigning Olympic champion Alexander Zverev in his opener.
Australian No.2 Alexei Popyrin, the world No.40, drew a qualifier but will likely strike 2023 Australian Open runner-up Stefanos Tsitsipas in the second round if he progresses.
Jordan Thompson, Jason Kubler, Thanasi Kokkinakis and wildcard Rinky Hijikata are also projected to play seeds in the second round at Flushing Meadows.
Australian No.1 Alex de Minaur was assured of avoiding a seed until at least round three after being seeded 13th.
De Minaur starts against a qualifier, with Chile's world No.24 Nicolas Jarry slated to be the 2020 Open quarter-finalist's first seeded opponent.
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