Nestor and Mirnyi were dominant and earned the victory in just under 90 minutes with a combined five aces. They won all 10 of their service games while breaking the South Americans twice from four chances.
The 39-year-old Canadian and his partner are seeded second in the doubles field behind Americans Bob and Mike Bryan, their longtime rivals. They will next take on Italians Potito Starace and Daniele Bracciale.
Nestor and Mirnyi reached the semifinal at Melbourne Park in 2011, with Nestor and his former partner Nenad Zimonjic of Serbia playing the 2010 final.
Milos Raonic of Thornhill, Ont., was due on as a showcase match when he faced local favourite Lleyton Hewitt in the singles third round. The No. 25-ranked Canadian will be playing on a Grand Slam showcase court for the first time in his career.