Markakis homered into the second deck in right field to give the Orioles a 2-1 win in 11 innings over the Nationals on Friday night.
Markakis' blast off Nationals reliever Ryan Mattheus (2-1) propelled Baltimore to its fourth straight victory. The first-place Orioles improved to 6-2 in extra innings with all six victories coming on the road.
"Hopefully, it bodes well mentally," Orioles manager Buck Showalter said of his team's late-game heroics. "When you get in those situations that you've been there and handled it well because, especially on the road, there's such a finality to that bottom of the inning. But the key is our guys are playing pretty loose through that. It's a loose clubhouse. They have a lot of confidence in close ballgames."
Facing the Nationals' fourth pitcher of the game and a 2-2 count, Markakis was not looking for a slider from Mattheus. That's what he got. As it turns out, he was ready for a pitch that Mattheus said "kind of hung" over the plate.
"I wasn't expecting that," Markakis said. "I put a good swing on that and went out of the ballpark."
Hits and runs were hard to come by for either side.
Four relievers followed Orioles starter Jake Arrieta, who matched his career-high with nine strikeouts. He allowed one run and six hits, walking one in seven innings.
Edwin Jackson matched him, allowing one run in eight innings with eight strikeouts and one walk.
"That was a tough one," said Nationals manager Davey Johnson, who previously played for and managed the Orioles. "It was a shame to waste such a great pitching effort by Jackson. He pitched outstanding."
Kevin Gregg (2-1) pitched the 10th inning for Baltimore and Pedro Strop worked the 11th inning for his third save. Three runners reached against Strop, but Ian Desmond hit into a double play and LaRoche grounded back to the mound with two runners on.
Arrieta entered the game having allowed 13 earned runs over his past two starts, including seven runs in 3 2/3 innings against Tampa Bay on Sunday. No signs of that pitcher existed in the series opener.
"(I) wanted to try to command multiple pitches in the zone, and when I got ahead just finish guys off," Arrieta said. "Not let the pitch count run up and try to pitch as deep into the game as I could."
Adam Jones drove home the Orioles' first run with a first-inning infield single against Jackson. Desmond tied the game with a solo home run in the sixth inning against Arrieta. It stayed that way until Markakis' final at-bat.
"We pitched good. Bullpen pitched good," Johnson said. "But one pitch -- ball game."
The 19-year-old Harper was 2-for-3 with a walk.
Xavier Avery led off the Orioles first inning with a walk and one out later moved to third on Markakis' double to left center. Jones sent a sharp grounder off Jackson's left heel. The ball caromed behind the mound, allowing Avery to score from third.
Jackson escaped further damage by inducing Wieters into an inning-ending double-play grounder. He then settled in, striking out the side in the second inning.
Held scoreless by Arrieta through five innings, the Nationals tied the game in the sixth on Desmond's sixth home run of the season, landing deep in the left-field stands.
This series between the neighboring franchises marks the first time since the Nationals moved from Montreal to Washington that both teams have winning records.
"I think the way rivalries start is with winning ballclubs," Arrieta said. "Both of these clubs, we're both playing extremely well. "
Jones extended his hitting streak to 10 games for third time this season. ... Nationals OF Michael Morse (back) is expected to begin an extended spring training assignment on Monday at the Nationals camp in Viera, Fla., manager Davey Johnson said. Morse has not played in a game this season. ... The Nationals' game against the Miami Marlins that was rained out on April 22 has been rescheduled as part of a doubleheader on Aug. 3. ... Saturday's pitching matchup pits Orioles RHP Jason Hammel against Nationals LHP Ross Detwiler.