Nationals pitcher Stephen Strasburg conceded just three hits and one run in his eight innings on the mound, while shortstop Ian Desmond finished with four RBIs and three hits from four at-bats, as the National League (NL) East-leaders cruised past the Diamondbacks.
Washington (71-53 win-loss record) have a six-game advantage in the NL East standings over the Atlanta Braves (66-60), who crushed the Pittsburgh Pirates 11-3 on Tuesday, while the Miami Marlins (63-62) are 2.5 games further back after a 4-3 extra-innings triumph over the Texas Rangers.
In Washington, Arizona started brilliantly with David Peralta thumping Strasburg 395 feet over centre field to give the visitors a 1-0 lead.
But that was as good as it got for the Diamondbacks with the Nationals scoring six runs in the third inning to take control of the match.
Desmond's single to left field saw the hosts take a 3-1 lead as Anthony Rendon and Jayson Werth both scored, while Washington's shortstop sent the same pair across home plate in the sixth inning to wrap up the Nationals' victory.
In Pittsburgh, Justin Upton and Evan Gattis both hit home runs as Atlanta won their fifth consecutive game.
Upton finished the game with five RBIs from four at-bats as the Braves destroyed Pittsburgh's starting pitcher Francisco Liriano.
Liriano was dragged after four innings having conceded 10 hits and nine runs.
Meanwhile, the Marlins needed 10 innings to overcome the Rangers, who came from 3-1 down to level the game in the seventh inning, before Giancarlo Stanton's single in the 10th saw Jeff Baker score for Miami.
In a high-scoring day in MLB, NL West-leaders the Los Angeles Dodgers held on for an 8-6 triumph over the San Diego Padres.
The Houston Astros defeated the New York Yankees 7-4, the Cleveland Indians trumped the Minnesota Twins 7-5, the Detroit Tigers needed 11 innings to overcome the Tampa Bay Rays 8-6 and the Kansas City Royals won 7-4 over the Colorado Rockies.
The Oakland Athletics cruised past the New York Mets 6-2, the Milwaukee Brewers clobbered the Toronto Blue Jays 6-1 and the Baltimore Orioles had few concerns against the Chicago White Sox, winning 5-1.
In other results, the Seattle Mariners defeated the Philadelphia Phillies 5-2, the Los Angeles Angels edged out the Boston Red Sox 4-3, the St Louis Cardinals prevailed