The Nationals, who won their first four games against the Marlins this season, lead the Majors with 18 earned runs allowed in the first inning.
"It's been difficult early on in some games when the starters have given up early runs and we've fallen behind," Nationals manager Matt Williams said.
One night after putting together the most complete game of a young season by pounding out 15 hits -- 11 for extra bases -- Washington collected just one through seven innings against righty Tom Koehler (2-1).
Strasburg (1-2), meanwhile, turned in his shortest outing of the young season and gave up a season-high six runs over four innings. Five days ago he went 6 2/3 and allowed one run with 12 strikeouts against Miami.
Like in the series opener, the Nationals had a two-out scoring opportunity in the first.
Anthony Rendon led off with a single before Bryce Harper grounded into a 6-3 double play. Koehler walked consecutive batters and threw a wild pitch to put runners at the corners, but Ian Desmond grounded into a fielder's choice to end the rally.
"It was a case of trying to do too much knowing that you have to go deep in the game and trying to be extra effective," said Koehler, who walked five and struck out three. "That's how you get in trouble. I had to step back and remember to make your pitches, take a deep breath and get back after it."
In the bottom half of the inning, Strasburg surrendered a three-run homer to Giancarlo Stanton to straightaway center. Stanton's fifth dinger of the season came on a 2-1 pitch. He now has three homers and eight RBIs against Strasburg.
The four hits allowed in the first were one more than the Marlins recorded in Strasburg's 6 2/3 innings last Thursday. Strasburg noticed guys being more aggressive early in the count against him. His location was also off throughout the game.
Over four 2014 starts, Strasburg has given up 14 earned runs on 24 hits in 21 innings.
"I think for me, if I can get through the first couple innings unscathed I'm pretty much able to shut the door from there," said Strasburg, who struck out five and walked three over 81 pitches. "The biggest thing is that pitch from Stanton. I've got to do a better job of executing that pitch. I can live with a couple runs here or there in the first, but that put me behind the eight ball."
Miami produced another three runs off Strasburg in the second on four hits and two walks.
Adeiny Hechavarria tripled to lead off the frame, Koehler struck out and Christian Yelich walked. Marcell Ozuna then drove in Hechavarria with an infield single to short, and Strasburg intentionally walked Stanton to load the bases. After Garrett Jones grounded into a forceout at home, Casey McGehee singled in two with a hit to left.
Benches and bullpens cleared when Desmond and Jarrod Saltalamacchia began jawing at each other following a high and inside pitch from Koehler in the fourth. Warnings were issued to both teams.
"The guy pitched a great game. I wasn't necessarily thinking he had intentions of hitting me," said Desmond, who went hitless in two at-bats. "You can drill me in the ribs, drill me in the leg -- wherever you want -- but four or five times missing in or around the head? I'm not claiming it's on purpose, but you've got to be able to control the ball. No big deal. It wasn't intended to escalate to what it did. Just heat of the moment stuff sometimes."
Craig Stammen came on in relief for Strasburg in the fifth -- giving up five runs on six hits -- as the Marlins extended their lead to 11.
His throwing error on Koehler's sacrifice bunt allowed Derek Dietrich and Hechavarria to score. Stanton drove in a pair with a double, and Jones capped Miami's scoring with an RBI single to right.
The Nationals avoided the shutout with a pair of runs off lefty Dan Jennings over the final two frames.
Harper singled with one out in the eighth and advanced to second on a wild pitch. He scored on a throwing error by Ozuna following Steven Souza's first Major League hit. Zach Walters, inserted into the game as a defensive replacement, connected on the first pitch from Jennings for a leadoff homer to right in the ninth.
"That's one of those [games]," Williams said of the blowout, "but nonetheless it's important that we play well. We didn't play well tonight."