The shock 2024 champion progressed in just 76 minutes, beating the 32nd-seeded Belgian Raphael Collignon 6-4 6-3 on Wednesday (Thursday AEST).
Former world No.19 but currently ranked 139, Popyrin beat fellow Australian Thanasi Kokkinakis to earn his place in the main draw and saw off Roman Andres Burruchaga in round one to notch his first ATP-level win since May.
And with another crack looming at the US Open in New York - where he beat Novak Djokovic in 2024 en route to his best finish at Flushing Meadows - Popyrin can largely credit another win in Canada to his booming serve.
"Popeye" fired down 10 aces, won 84 per cent (27/32) of first-serve points and didn't face a break point, while also converting on three-of-nine break-point opportunities of his own.
The Sydneysider will next face another Argentine in Thiago Tirante, who upset world No.9 and seventh-seeded American Taylor Fritz 7-5 6-3.
At the women's WTA event in Toronto meantime, Aussie qualifier Maya Joint has joined compatriot Talia Gibson in the third round after taking down 14th seed Sorana Cirstea.
Joint, the 20-year-old Michigan-born world No.69, won 6-4 6-4 to set up a clash with Russian Liudmila Samsonova.
After dropping serve to trail 3-1 in the first set, Joint won five of the next six games to take it in 45 minutes.
Both players were broken twice inside the opening six games of the second set, before the Romanian dropped serve again in the seventh game and Joint powered to victory.
Earlier, Australian world No.61 Daria Kasatkina suffered a 6-3 5-7 6-4 loss to second seed Elena Rybakina.
The two-time grand slam champion from Kazakhstan, who had a first-round bye, survived after a two-hour 22-minute scare to progress and tee up a clash with 28th seed, Anna Li of the US.
"She's a tough opponent," Rybakina, who hit 58 winners and had as many unforced errors, said of Kasatkina.
"And for the first match it wasn't too bad, but of course I want to improve."