Strasburg sent an 0-2 pitch from Wei-Yin Chen into the Baltimore bullpen in the fourth inning to put the Nationals ahead 5-3. After dusting off his home run trot and returning to the dugout, Strasburg responded to a curtain call by waving to the crowd of 41,918.
The hard-throwing Strasburg had five hits in 40 big league at-bats before Sunday. He singled and scored in the third inning, then followed a shot by Jesus Flores with one of his own in the fourth.
Known more for his pitching than his hitting, Strasburg (4-1) excelled at both. The right-hander allowed three runs, one earned, four hits and a walk in his first career appearance against Baltimore. He retired the last 10 batters he faced.
Since returning from elbow ligament replacement surgery last September, Strasburg is 5-2 with a 1.99 ERA in 14 starts.
Danny Espinosa also homered, and Bryce Harper drove in two runs and scored three to help the Nationals avert a three-game sweep by their regional rivals.
Chen (4-1) yielded six runs and eight hits in 4 1-3 innings and absorbed his first major league loss. The Taiwan native was vying to become the first Baltimore starter to begin his Orioles career with five straight wins since Jimmy Key in 1997.
The loss ended Baltimore's five-game winning streak and nine-game road run. The Orioles scored the game's first three runs but got only two hits after the second inning - both in the ninth.
Baltimore went up 1-0 in the first when Xavier Avery walked, advanced on a fly ball and scored on a single by Nick Markakis.
The Orioles added a pair of unearned runs in the second after Harper drifted from center to left field to chase down a wind-blown fly ball, then dropped it. Robert Andino drove in a run with a groundout and Avery added an RBI single before Strasburg struck out J.J. Hardy with two outs and runners on second and third.
Harper made amends in a three-run third. Strasburg singled, Espinosa doubled and Harper hit a liner to right that a diving Markakis gloved but lost when he hit the ground. The triple scored two runs, and Harper scored on a groundout by Ian Desmond.
Flores gave Washington a 4-3 lead with his first homer since Aug. 18, and that only served as a prelude to Strasburg's clout.
Desmond chased Chen with an RBI single in the fifth, and Espinosa homered with a runner on during a three-run eighth.
NOTES: Orioles C Matt Wieters, who had the day off after a night game, will have to wait until Monday to try and snap an 0-fror-18 slump. ... Tommy Hunter (2-2) takes the mound for Baltimore on Monday night in the opener of a three-game series against visiting Boston. ... Gio Gonzalez vies for his sixth win when the Nationals open a nine-game road trip Monday in Philadelphia. ... Avery got his first major league stolen base. ... Washington Capitals forward Jason Chimera fired a strike with the ceremonial first pitch.