Belarusian Azarenka, who won her two Grand Slam titles in Melbourne in 2012 and 2013, started the stronger and looked to be in complete control, the 12th seed racing to a 5-2 lead in the first set.
However, things quickly fell apart as American Pegula, the world number 61, took the next five games to seal the set.
Fearless 💪@JLPegula breaks through to the second round after overcoming a Victoria Azarenka sized challenge 👏7-… https://t.co/y1bMIMozsS
— #AusOpen (@AustralianOpen) 1612841434000
Azarenka’s troubles continued in the second set and she took a medical timeout while trailing 4-2 after appearing to have trouble breathing.
She returned to hold serve and followed that up with a break to draw level at 4-4, but Pegula broke straight back before serving out the match, sealing victory with an ace.