Second baseman Danny Espinosa crushed a home run to left on a 1-1 pitch off Padres' starter Clayton Richard leading off the bottom of the fifth, giving the Nationals a 1-0 lead.
It was only the Nationals' third hit off of Richard and the seventh homer on the season for Espinosa, a new career-high.
It was the first homer this season for Espinosa with nobody on base. Each of his other six round trippers have been multi-run HRs.
John Lannan has allowed only one hit through five innings with four strikeouts and one walk.
The game had a 47-minute rain delay during the fourth inning.