Nick Hundley went 3-for-4 with a two-run homer, 6, to avoid getting swept by the NL game series.
Chris Young and Collin Cowgill had two-run hits during the sixth inning for Arizona, whose division lead over San Francisco was trimmed to 8 1/2 games. The Giants beat the Dodgers on Sunday, and the Diamondbacks' magic number is still eight.
Josh Collmenter (9-9) took the loss after allowing six runs in four-plus innings.
Hundley doubled and scored on James Darnell's base hit in the second inning, and the Padres tacked on three runs in the third.
LeBlanc led off with a single and moved to third on a ground-rule double by Cameron Maybin. LeBlanc was tagged out at home trying to score on a ball hit to short by Chris Denorfia, but Guzman followed with an RBI single.
The runners advanced to scoring position on the throw, and a walk to Hundley loaded the bases. Collmenter walked in a run before Darnell hit a sacrifice fly.
Collmenter walked Guzman to open the fifth before Hundley's two-run blast to left chased the Arizona starter. Guzman's RBI single off Zach Duke in the sixth increased the San Diego lead to 7-0, and at that point it was a matter of holding on.
Henry Blanco began a five-run rally in the bottom half with a leadoff homer to left.
The Diamondbacks had two on with two away later in the inning, and LeBlanc prolonged the inning with a walk to Paul Goldschmidt. He was replaced by Erik Hamren, but Hamren couldn't avoid giving up damage.
Chris Young smacked a two-run double and Cowgill followed with a two-run single, bringing Arizona within 7-5.
The Diamondbacks were within a run in the seventh, when pinch-hitter Justin Upton's grounder plated Blanco.
But San Diego held on. Luke Gregerson came in to get the final out of the inning, then pitched a scoreless eighth. Heath Bell worked around a leadoff walk to Willie Bloomquist in the ninth to record his 37th save.
San Diego improved to 1-3 on its road trip, which ends with a three-game set in San Francisco starting Monday...Arizona starts a six-game trip in LA on Monday. After three games there, the D-Backs head to San Diego...Arizona still leads the season series, 10-5...Collmenter suffered his first loss since August 21, when he allowed a run in seven innings to Atlanta. He hadn't given up six runs since August 5, when he lasted 2 1/3 innings against the Dodgers...LeBlanc snapped a three-start losing streak.