Lane Thomas hit his second home run of the game in the 10th inning, a two-run rip off Alexis Diaz, to hand the Reds their fourth straight defeat.
After taking three straight beatings from the Chicago Cubs in Wrigley Field, the Reds jumped to an early 3-0 lead on solo home runs by Nick Senzel, Matt McLain and Elly De La Cruz.
Reds starter Graham Ashcraft had the Nationals nuzzling from his hand. He gave up a home run to Thomas in the sixth inning, but the Reds still led by 3-1.
Thomas came into the game mired in a deep slump, 3 for 26 with 13 strikeouts.
Ashcraft, though, took that 3-1 lead into the eighth inning and had given up only three hits.
But with two outs and nobody on, Thomas reached on an infield hit and Joey Meneses tied it with a home run into the left-field seats.
The Reds had a chance to end it in the bottom of the ninth when Joey Votto led with a full-count walk. TJ Friedl ran for Votto and with one out he stole second.
Tyler Stephenson was walked intentionally and Friedl stole third. Stuart Fairchild struck out for the second out and the Nationals wisely walked De La Cruz intentionally, filling the bases.
With right-hander Andrew Machado on the mound, manager David Bell chose to permit right-handed Senzel to bat instead of using left-handed Jake Fraley to pinch-hit.
Senzel popped meekly to second base, sending the game into extra innings.
In the 10th, Diaz gave up a double to Jake Alu that scored automatic runner Lldemara Vargas from second for Washington’s first lead of the game, 4-3.
With two outs, Thoms struck again, deep into the lungs of the Reds, with his two-run dagger.
Nats closer Kyle Finnegan made quick work of the Reds in the bottom of the 10th by striking out McLain, who had three hits, striking out Spencer Steer and coaxing a game-ending ground ball from Kevin Newman.
The Nationals (47-63) are 4-1 in extra-inning games and the Reds are 7-5.
Senzel and McLain went back-to-back with one out in the first against Washington left-hander Patrick Corbin.
Senzel poked his 350 feet down the right-field line, his fourth hit and second home run against Corbin. One pitch later, McLain blasted a no-doubt 422-footer over the center field wall.
De La Cruz made it 3-0 with a line drive into the left-field seats, his ninth of the season, but his first batting right-handed.
While Ashcraft was in complete control, he received above-and-beyond defensive help from center fielder Fairchild.
Fairchild encountered some difficulty defensively in Wrigley Field but made up for it Friday. First, he crashed into the center field wall in the third to snag a CJ Abrams long drive. And in the sixth he made a diving, rolling catch of a blooper hit by Meneses.
But it all came apart in the eighth and 10th inning for the Reds as Washington scored six unanswered runs.
Corbin gave up only four hits in 6 1/3 innings, but three were home runs. After the third inning, the Reds had only three more hits.
One was a one-out double in the sixth by McLain, but Steer and Newman both launched fly ball outs.