San Diego sent 22 men to the plate over the first two frames while scoring 13 runs on 14 hits. The Padres produced 20 hits overall while running up their largest run total of the season.
After Will Venable opened a four-run first with a solo homer, Ludwick had a two-run double and Guzman contributed an RBI single.
San Diego smashed the Marlins with nine second-inning runs. Three of them scored on a double by Guzman and two more came in on a single by Ludwick.
Guzman, Jason Bartlett, Rob Johnson and Cameron Maybin all had three hits to make things easy for Aaron Harang in his 250th career start.
Harang (8-2) gave up three runs on seven hits over 5 1/3 to get the win, his fourth straight. Ricky Nolasco retired only four batters while taking the loss. He was charged with nine runs on nine hits.
Florida third baseman Emilio Bonifacio extended his career-best hitting streak to 19 games.