The 23-year-old Popyrin, ranked at 90 in the world, came through 6-7 (5/7), 6-3, 6-4 after two hours and 36 minutes on court to claim a second career title to add to his 2021 Singapore victory.
Three-time major winner Wawrinka, 38, was hoping to capture a 17th career title but first since Geneva in 2017.
Wawrinka recovered from 3-5 down in the opening set before claiming the tie-breaker.
Popyrin, 15 years Warinka’s junior, levelled by pocketing the second set and was a break ahead in the first game of the decider which he immediately handed back.
The young Australian twice required assistance from the trainer in the third set but carved out the key break in the ninth game before serving out for victory.
Despite defeat, former world number three Wawrinka will return to the top 50 next week having fallen out of the top 300 after undergoing two surgeries on his feet in 2021.
