Espinosa hit a three-run shot to cap the Nationals' five-run third inning, and added another solo blast in the sixth, his 10th of the season. It was the second multihomer game of his career. He also hit two against the New York Mets on Sept. 6, 2010.
Michael Morse added two RBI on three hits for Washington, which snapped a six-game losing streak against the Phillies and won for just the second time in the past 10 games.
Domonic Brown and John Mayberry hit back-to-back homers to lead off the fifth inning for Philadelphia. It was the second consecutive game - and the second time this season - the Phillies had back-to-back home runs.
Jason Marquis (6-2) gave up two runs on eight hits, struck out four and did not allow a walk in 6 1-3 innings. It was his first win against Philadelphia since joining the Nationals for the 2010 season. In his previous six starts against the Phillies, Marquis was 0-5 with a 9.49 ERA in 24 2-3 innings.
Cliff Lee (4-5) allowed six runs on seven hits, walked three and struck out four in 5 1-3 innings. The six runs tied his season high.
The Nationals opened up a 5-0 lead in the third inning. After loading the bases with one out, Jayson Werth drove in the first run with a sacrifice fly. Morse followed with a run-scoring single, and Espinosa finished things off with his three-run home run into the left-field visitor's bullpen.
Washington added three more runs in the seventh on Morse's RBI double and run-scoring singles by Ivan Rodriguez and Jerry Hairston. Werth's RBI double in the eighth put the Nationals in double digits for the second time this season.
Brown opened the fifth inning with his first home run of the year to right field, and Mayberry followed with a drive to left for his third homer. Brown also added a double in the seventh inning.
NOTES: Philadelphia recalled LHP Mike Zagurski from triple-A Lehigh Valley Tuesday. Zagurski pitched the eighth inning, allowing one run. The move filled the roster spot opened when RHP Vance Worley was optioned to Lehigh Valley after Monday's game. In his last start Sunday, Worley allowed eight runs, five earned, over three innings against the Mets. Pitching coach Rich Dubee said Kyle Kendrick would take Worley's rotation spot for Saturday's game at Pittsburgh. ... CF Shane Victorino (right hamstring strain) is expected to come off the disabled list later this week, and Philadelphia coach Charlie Manuel was noncommittal about a corresponding roster move. Manuel did indicate that the team could carry eleven pitchers on its roster rather than the customary twelve. ... The Nationals rescheduled their May 17 game against Pittsburgh, postponed due to rain, as part of a July 2 doubleheader. ... 3B Ryan Zimmerman will play in an extended spring training game Wednesday, his first action since undergoing abdominal surgery in early May.