To set Jordan Zimmermann up with an early cushion, the middle of the Nationals' order dialed up the longball with two outs in the first.
Ryan Zimmerman took Scott Kazmir deep before Jayson Werth made it back-to-back homers for a 2-0 Nationals lead.
It was Zimmerman's eighth of the season and second in three games after an 11-game drought. Werth hit his sixth of the year.
The Nats have hit back-to-back homers four times this year and now hit at least one longball in 79 consecutive series for the longest active streak in baseball - also franchise and D.C. baseball records.
That could bode well for Zimmermann, who hasn't surrendered an earned run over 15 innings in his last two starts. The right-hander enters the contest with a 2.00 ERA, having permitted more than two runs just twice in 13 starts.
Update: Ian Desmond made it three Nats homers off Kazmir by starting the second with a solo shot to left, upping the lead to 3-0. It was Desmond's ninth of the year.
And the Nats had hit as many homers as Kazmir had recorded outs by the time he retired a batter in the second.
Update II: After clearing the fence three times in the first two frames, the Nats rallied to increase their lead to 5-0 in the third, giving Kazmir a quick hook.
Kazmir lasted just 2 2/3 innings, allowing five runs on four hits and four walks while striking out two.
Anthony Rendon started the third with another double, his fifth in eight games since being called back up. Zimmerman and Werth kept their back-to-back trend going, this time by drawing two straight walks to load the bases.
Rendon came in to score when Adam LaRoche grounded into a double play that nearly was a pretty conventional triple play. But Zimmerman's slide into third beat the throw from first, keeping the inning alive.
Zimmerman scored on Kazmir's final toss of the game, a ball-four wild pitch to Desmond. The pitching Zimmermann has held the Indians to no hits and one baserunner through two innings.
Update III: Zimmermann's line took its first hit, literally, in the third.
Mike Aviles doubled with one out for the Indians' first knock and scored on Jason Kipnis' RBI single two batters later, cutting the Nats' lead to 5-1.
Update IV: Make that three starts that Zimmermann has allowed more than two runs this season.
The Indians came up with back-to-back homers of their own with two outs in the fourth - by Carlos Santana and Mark Reynolds - to narrow the Nats' lead to 5-3. The ball is just flying out of Progressive Field with five homers in the first four innings.
It marks the first time that Zimmermann has given up multiple homers in a game since Sept. 1, 2012, ending a streak of 18 straight games holding opponents to one or fewer.