Zimmerman's bases-loaded blast highlighted a six-run third inning that gave the Nats a 7-1 lead. The Washington third baseman has racked up 12 RBI in his last 10 games.
Rendon supplied a two-run homer and an run-scoring single while Bryce Harper went 3-for-4 with an RBI as the Nationals reeled off a fourth straight victory overall.
Stephen Strasberg (5-6) allowed four runs on seven hits over six innings to record the victory.
Padres starter Robbie Erlin (1-2), meanwhile, was lit up for nine runs on six hits over four full frames.
Alexi Amarista went 3-for-5 with a two-run homer and three RBI while Chase Headley also provided three hits and drove in a run for San Diego, which dropped a ninth straight contest.