The Australian was far from his best and even suffered a rare break of serve but his booming serve and thunderous forehand ultimately overpowered the Argentine.
Kyrgios has won 13 of his last 14 matches with his only loss coming at the hands of Novak Djokovic in the Wimbledon final in June.
Kyrgios and Medvedev both entered the Masters 1000 tournament in Montreal after notching titles at U.S. Open tune-up events.
Kyrgios won the Citi Open in Washington D.C. for a second time last weekend while Medvedev did not drop a set en route to lifting the trophy in Los Cabos. "Medvedev is coming from a title too and he is the number one in the world," said Kyrgios, who holds a 2-1 head-to-head lead over the Russian. "It's not like the rankings mean too much as the guy I played today is ranked ahead of me.