In a provocative and steamy routine, Virtue and Moir – who became a hugely popular pairing from their performances at the Vancouver Olympics – excelled with their "Carmen" routine on home ice.
The 23-year-old Virtue and 25-year-old Moir scored 104.32 points for their free dance, bringing the crowd at the WFCU Centre to its feet.
The pair finished with 169.41 overall.
Italian pairing Anna Cappellini and Luca Lanotte won the silver with 160.06, while Russian duo Ekaterina Riazanova and Ilia Tkachenko won bronze with 143.39.
Javier Fernandez stunned Patrick Chan in the men's event in Windsor, Ontario.
Fernandez, who became the first Spanish skater to win a Grand Prix medal when he won silver at the 2011 Skate Canada, finished 10.5 points ahead of the two-time defending world champion.
Chan struggled with his jumps and received 160.91 points for his La Boheme-themed long programme. His combined total was 243.43 was well behind Fernandez who extended the lead he established in the short programme.
The home fans did have something to cheer as 16-year-old Kaetlyn Osmond overcame Georgia's Elene Gedevanishvili to win the women's event.
Osmond scored 115.89 points for her Carmen rendition and 176.45 overall to take victory on her Grand Prix debut.
Reigning world bronze medallist Akiko Suzuki was second with 175.16 while Japanese team-mate Kanako Murakami was third with 168.04 with Gedevanishvili, double bronze medallist at the European Championships, dropping to fifth after an error-strewn routine.
Germans Aliona Savchenko and Robin Szolkowy, the quadruple world champions, completed a comfortable victory in the pairs.