He got things going with a grand slam in the bottom of the third, putting the Blue Jays up 4-3.
The hit snapped a streak of 17 scoreless innings for Nationals starter Max Scherzer.
But the onslaught wasn't over. Guerrero launched a solo shot in the bottom of fifth to increase the distance to 7-3, then logged a two-run shot in the bottom of the seventh.
The first baseman now has seven home runs on the season, putting him one off the league lead that is currently held by Ronald Acuna and Rhys Hoskins. He launched nine in the pandemic-shortened 2020 campaign and had 15 as a rookie through 123 games in 2019.