Rendon hit a solo shot in the first, and Jayson Werth, Ian Desmond and Wilson Ramos also connected against Hernandez (13-5). It was the first time Hernandez has allowed four homers in a game.
Werth's two-run shot in the third gave the Nationals a 3-2 lead and Desmond added his 22nd an inning later.
Bryce Harper and Ramos went deep in the eighth against Joe Beimel.
Jordan Zimmermann (10-5) struck out eight in six innings for Washington.