Left-hander Gio Gonzalez pitched well enough to win, but the two-run, 32-pitch first inning proved to be his undoing.
The Nationals put two runners on in the ninth, but catcher David Ross picked off Clint Robinson at first base to end the game.
The Nationals have lost six out of their seven games, while the Cubs snapped a two-game slide and improved their record to 28-24.
MOMENTS THAT MATTERED End with a bang: Anthony Rendon was batting with the tying and winning runs on base in the ninth inning, but the game ended with the bat on his shoulders. Clint Robinson, who marked the winning run at first base, was picked off by Ross with two outs. First baseman Anthony Rizzo called the play, and Ross answered with a bullet to close the door. More >
"I'm always looking for that," Rizzo said. "He's just getting off big there, and he's the tying run so he's getting a big, aggressive secondary lead. Rossy gave me a look and confirmed the sign and made a good throw."
Starting early: The Cubs wasted no time jumping on Gonzalez. The first two batters of the game, Dexter Fowler and Kris Bryant, both reached -- Fowler via single, Bryant via walk -- and scored to provide Chicago with an early 2-0 lead. Fowler scored the game's first run on a Junior Lake walk, and Bryant came around when Starlin Castro grounded into a 6-4-3 double play.
The bats are cold: The Nationals scored their only run in the sixth inning. Denard Span scored on a groundout by Bryce Harper. Harper nearly beat the play out, but the Nationals lost their challenge earlier in the game and could not get a review of the play. It ended 18 straight scoreless innings. The last time they scored prior to Thursday was the fifth inning during the second game of a doubleheader against the Blue Jays. Max Scherzer scored on a sacrifice fly by Tyler Moore. In their last seven games, the Nationals are hitting .226 with a homer, 15 RBIs and .303 on-base percentage. More >
"We are not going to get that detailed about it," Nationals manager Matt Williams said. "We had opportunities, so we are going to try to create those opportunities. There are ebbs and flows to seasons in every aspect -- pitching, defense, offense ... If we continue to create those opportunities and we have chances to win games. As of tonight, it didn't happen for us."
Gio has quality start: Gonzalez suffered his second consecutive loss tonight. He pitched six inning and allowed two runs on four hits. His only blemish came in the first inning when he allowed the two runs on 32 pitches. Gonzalez had to make a mechanical adjustment after the inning. He was flying open in the first inning.
"I didn't throw strikes [in the first inning]. The second inning I threw strikes, that was the difference," Gonzalez said. "I walked two batters in an inning. It can haunt you. After that, you turn that page, you settle down, pound the strike zone."
"I've just got to give [David Ross] a lot of credit there, and actually Anthony [Rizzo] to put the play on. I love it. Absolutely love it. If he had thrown that ball down the right-field corner, I would've been fine. I would've been absolutely fine with the whole play because it was the right thing to do." -- Cubs manager Joe Maddon, on the game-ending pickoff at first base
"I got too far -- ballgame. It's pretty much plain and simple. It's frustrating. That's on me. That can't happen. I took the bat out of Anthony's hands. He is one of our better hitters. That's just on me. That can't happen. I really can't explain it. I wasn't really trying to go anywhere. I just couldn't get back fast enough." -- Robinson, on being picked off first base to end the game
UPON FURTHER REVIEW
In the fourth inning, Danny Espinosa was called out at second base on a steal attempt. Espinosa protested that he beat the tag, and the Nationals challenged the play. After two minutes and 34 seconds, the play was confirmed.
WHAT'S NEXT Cubs:Tsuyoshi Wada will face the Nats for the second time in two weeks Friday night at 6:05 p.m. CT at Nationals Park. Wada lasted 5 1/3 innings and allowed one run in his previous outing against Washington, but did not factor in the decision.
Nationals:Tanner Roark will be on the mound when the Nationals face the Cubs in the second of a four-game series at 7:05 p.m. ET on Friday. Roark has made two starts in place of the injured Doug Fister (right forearm), and has done well in both. He has allowed three earned runs in 11 innings. Roark is 2-2 with a 5.03 ERA in his career against the Cubs.
Bill Ladson is a reporter for MLB.com and writes an MLBlog, All Nats All the Time. He also can be found on Twitter @WashingNats. Jacob Emert is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.