Harper left the ballpark first. Trea Turner led off the game with a flyout to right field. Harper then stepped up to face Orioles starter Dylan Bundy. The right hander threw a 91.2-mph four-seam fastball with his first offering and Harper swung away.
He connected with the pitch and sent it deep to right center field. The shot traveled 399 feet and left Harper's bat at 101-mph, according to Statcast. Harper now has a National League leading 17 home runs this season.
The Nationals did not score again in the inning, leaving room for Machado to answer back quickly.
Washington starter Jeremy Hellickson struck out Jonathan Schoop to start the bottom of the first frame. Adam Jones then hit a ground out. Machado took a called strike on the following pitch from Hellickson, before working the count to 2-1.
He jumped all over Helickson's fourth offering, a 77.6-mph knuckle curve. Machado belted the knee high pitch deep to left field, putting the shot just over the outfield fence. The Orioles shortstop now has 16 home runs this season.
Wilmer Difo hit an RBI single in the second inning and Mark Reynolds went yard in the fourth frame to give the Nationals a 3-1 lead. Adam Jones closed the gap with an RBI double in the fifth inning. The Nationals led 3-2 after six innings.
Harper was 3-for-3 with an RBI and a run scored, while Machado was 2-for-3 with an RBI, a run scored and a strikeout entering the seventh inning.