Hernandez, who stepped in for Blue Jays star Bo Bichette, went 2 for 5 with two RBIs in the 4-1 triumph at Nationals Park. He sent the second pitch of the game to deep right center field for a 413-foot solo home run.
Rowdy Tellez and Danny Jansen added solo homers in the fourth inning to push the Blue Jays' lead to 3-0. Kurt Suzuki plated the Nationals' lone run with an RBI double in the fourth frame.
Hernandez returned to the plate in the top of the next inning and hit his second long ball of the contest. The Blue Jays outfielder also settled in against starter Anibal Sanchez for that exchange.
Sanchez fell behind 2-0 in the count before Hernandez fouled off an 80.8-mph splitter. Sanchez then heaved in an 88.4-mph slider, which Hernandez hacked to right field for a 399-foot homer. The solo shot had an exit velocity of 104.2 mph.
Jansen and Hernandez were the only Blue Jays to collect multiple hits in the win. Jansen was 2 for 4 with an RBI and a run scored. The Nationals outhit the Blue Jays 11-7, as Trea Turner, Starlin Castro, Kurt Suzuki and Victor Robles each collected two hits in the loss.
Blue Jays starter Trent Thornton allowed eight hits and one run, but was not given a decision for his effort. Relief pitcher Ryan Borucki earned the win after he allowed one hit and no runs in 1.1 innings for Toronto.
Sanchez took the loss after he allowed six hits and four runs in five innings for Washington.
Bichette missed Monday's game due to tightness in his left hamstring. The Blue Jays shortstop is day-to-day due to the ailment.
The Nationals next host the Blue Jays in the second game of the series at 6:05 p.m. EDT Tuesday at Nationals Park.