Moncada hit his 11th home run of the season in the top of the second inning during the 9-5 loss on Tuesday at Nationals Park in Washington, D.C. The blast gave the White Sox a 5-0 edge at the time.
Chicago drew first blood on an RBI single from James McCann in the top of the first frame. Eloy Jimenez and Yolmer Sanchez followed with RBI singles, giving the White Sox a 4-0 advantage in the first inning.
White Sox starter Reynaldo Lopez escaped the first inning unscathed. Leury Garcia began the second inning with a strikeout, prompting Moncada's walk to the plate. The White Sox infielder fell behind 0-2 in the count against Nationals starter Stephen Strasburg before smashing the right-handed pitcher's third offering over the right center field fence.
Moncada's solo mash had an exit velocity of 112.5 mph and a launch angle of 26 degrees, according to Statcast.
Anthony Rendon plated the Nationals' first two runs with an RBI double in the third frame. Howie Kendrick hit a solo shot for Washington in the fourth inning. Rendon returned for a three-run homer in the fifth inning, giving the Nationals a 6-5 lead.
Howie Kendrick plated another run with an RBI double, before Victor Robles hit a two-run shot in the same inning for the Nationals' final two runs.
Moncada was 1-for-3 with two runs scored, two walks, two strikeouts and an RBI in the loss. He is now hitting .284 with 11 homers and 36 RBIs on the season.
The Nationals host the White Sox in the final game of the series at 1:05 p.m. on Wednesday at Nationals Park.