Vladimir Guerrero Jr. hit a two-run homer off Shohei Ohtani, and Addison Barger contributed with two hits and an RBI for the Blue Jays.
Blue Jays pitcher Shane Bieber delivered a strong performance, allowing just one run on four hits into the sixth inning after returning from Tommy John surgery.
Shohei Ohtani, pitching for the Dodgers, yielded six hits and four runs into the seventh inning and went 0 for 3 at the plate.
The victory ensures the World Series trophy will be decided at the Rogers Centre, with Game 5 scheduled for Wednesday at Dodger Stadium.