The Nationals had opened the season with consecutive shutouts but the Marlins finally got on the board with Justin Ruggiano's opposite-field home run in the second inning.
However, Ryan Zimmerman had already knocked in two runs with a first-inning double so Washington still has yet to be behind this season.
The Nationals added an RBI single by Bryce Harper in the third inning and a long drive to center by Werth in the sixth for a three-run home run.
Miami's Wade LeBlanc (0-1) allowed the first three Washington runs while Mike Dunn threw the pitch Werth hit out.
Jordan Zimmermann (1-0) allowed eight hits but only Ruggiano managed more than a single. He walked two and struck out one over six innings. The Washington bullpen contributed three innings of no-hit relief.