The local hope battled to make inroads on the Halys first serve, losing 5-7 6-3 6-4 in just less than two hours on Monday at Pat Rafter Arena.
His loss followed compatriots James Duckworth and Dane Sweeny's first-round defeats at the Australian Open lead-up event.
In the late match, top seed and former world No.1 Daniil Medvedev, who has slipped to No.13, looked ominous in a 6-2 6-3 drubbing of Marton Fucsovics as he attempts to climb that mountain again.
The Russian, a three-time Australian Open finalist, will play Frances Tiafoe in the second round after the American beat Australian Aleksandar Vukic on Sunday.
Popyrin was also ousted in the first round in 2025 before losing his opening clash at Melbourne Park in a year when his ranking fell from the mid-20s to now it's current mark of 50.
The 26-year-old began well, pressuring to break at 5-5 then serve out the first set.
But he was broken at the first attempt in the second and third sets and didn't win more than one point on the Halys serve until late in the decider.
Halys, ranked as high as 46 last year, landed 73 per cent of his first serves and won 90 per cent of them (52-of-58).
Earlier Sweeny, a lucky loser in the main draw after Brazilian young gun Joao Fonseca's withdrawal with a back strain, did his best to stay with 211cm American Reilly Opelka in a 6-3 7-5 loss.
The Australian, giving up 41cm to Opelka, could only smirk as he grabbed a plastic chair and stood on it at the net to shake hands, even then barely taller than the victor.
Opelka, on his injury return, beat Novak Djokovic en route to the Brisbane final last year before withdrawing early in the decider.
Duckworth led by a set and 2-0 in the second-set tiebreak, only to fall 7-6 (7-4) 6-7 (2-7) 6-3 to American talent Alex Michelsen.
Defending champion Jiri Lehecka was pushed in his centre court return against Tomas Machac 6-4 6-7 (5-7) 6-2.Â
He'll play Sebastian Korda in the second round, the American triumphant against Valentin Vacherot 7-6 (7-1) 6-3.
Nick Kygrios, a winner in Brisbane in 2018, will play Aleksandar Kovacevic on Tuesday.
There will be at least one Australian male in the second round, with Rinky Hijikata and Adam Walton to also duel it out on Tuesday.
