Jackson (4-4) allowed just one run on four hits and a walk with five strikeouts to capture the win, saying afterward that he approaches every day he pitches like he's the No. 1 starter.
"You have to be No. 1 on the day you pitch regardless of who you're pitching against," he said. "Numbers are numbers."
Mike Gonzalez finished the seventh, Sean Burnett tossed a scoreless eighth and Tyler Clippard nailed down his 12th save of the season with a 1-2-3 ninth.
Adam LaRoche laced a solo home run and Xavier Nady picked up an RBI with an infield single for the Nationals, who have won three of their last four games.
Adam Jones homered for the O's, losers in four of their last five.
Wei-Yin Chen (7-3) allowed three runs -- two earned -- on six hits and two walks with four strikeouts over five innings to take the loss.
The Nationals opened the scoring with a pair of runs in the second inning. Michael Morse and LaRoche hit consecutive singles and both runners advanced on a ground out by Ian Desmond. After Tyler Moore struck out, Nady beat out an infield single to score Morse, and LaRoche crossed the plate thanks to a throwing error by Orioles third baseman Wilson Betemit.
LaRoche crushed a fastball over the wall in right-center leading off the fourth to extend the lead to 3-0.
Jones was Baltimore's first baserunner after he reached on an error by the usually sure-handed Ryan Zimmerman to lead off the fifth and Betemit got the first O's hit of the game two batters later with a single to put runners on the corners with one down. Jackson fanned Mark Reynolds, but walked Nick Johnson to load the bases for Steve Pearce, who popped out, keeping the Orioles off the board.
"Hitting's contagious," said Jones, "and we're just not swinging the bats as well as we want to. ... It happens. Edwin threw a great game. I was just texting him right now. He threw a really good game and sometimes you just have to tip your cap to the man."
The Orioles finally cracked the scoreboard in the seventh after Jones led off by crushing a hanging slider from Jackson over the wall in left for his 19th homer of the season.
Clippard retired Chris Davis, Jones and Matt Wieters in order to lock down the victory for Washington.
Prior to Saturday's game, the Orioles released pitcher Jamie Moyer at his request. Moyer was picked up by Baltimore after being let go by the Colorado Rockies, but never made it to the major league level for the O's...Washington went 1-for-8 with runners in scoring position and stranded seven, while Baltimore finished 0-for-3 with men in scoring position and left four on base...The Nats improved to 10-7 in interleague play this season.