The Nationals battled back to tie but were unable to take the lead late against the Cubs.
Down 3-1, the Nats scored on a pair of sacrifice flies to tie the game heading to the ninth.
After getting through the eighth, left-hander Sammy Solis ventured out to pitch the ninth.
The Cubs opened with an Addison Russell walk. David Ross moved him up to second with a sac bunt.
Rookie Albert Almora Jr. then broke the tie with a run-scoring double.
The Cubs went on to win 4-3, handing Solis his second loss of the season.
Solis said giving up the go-ahead hit is bad, but the base on balls to begin the rally stung.
"Leadoff walk," Solis said. "I can't do that, especially in a game like that. This hitting team, I can't give them any type of edge. No outs, man on first. It hurts."
Nationals closer Jonathan Papelbon is on the disabled list with a intercostal strain on his right side.
Manager Dusty Baker will now have to decide who will close out games. On Tuesday, he opted to go with Solis for two innings.
Prior to the go-ahead run, Solis had gone 11 games without allowing a run, a span of 15 1/3 innings.
"He's been great for us," Baker said. "He just made one bad pitch. He got the slider up, and that was really the only bad pitch he's made in I don't know how long. He could've popped it up, he didn't miss it."
But even with his ERA now at only 1.71, Solis was taking this loss pretty hard.
"It was bad for me," Solis said. "It sucks to come out on that end. I just got to execute pitches better. I left a couple over the middle. Leadoff walk doesn't help. It's on me. I'll get them next time."
Center fielder Ben Revere said Solis will bounce back. There is a reason why Solis has stayed with the team since he was called up back in late April.
"It's baseball. He threw a good pitch, guy made a great hit, hit it in right spot," Revere said. "Nothing you can do. I told him just keep your head high. He's going to come back. He's been one of our best relievers since he got called up from Syracuse.
"We are going to need him. Maybe tomorrow or, of course, the rest of the year. Keep your head high, battle back. He's going to win a game for us down the road."
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