Cubs starter Travis Wood took a two-hit shutout and 2-0 lead into the eighth but Guzman reached on an infield hit and by the time the Cubs got out of the inning, the Padres had five hits, two walks and a hit batter that combined for four runs.
Wood (2-2) retired the first 14 San Diego batters and faced one over the minimum through seven innings. Guzman's single was followed by a walk to Kyle Blanks. Wood got two outs but Yonder Alonso singled in a run.
Shawn Camp replaced Wood bug a passed ball, on which Blanks reached home, tied the score at 2-2. Camp walked Chris Denorfia and was pulled for James Russell, whose second pitch was hit into center for an RBI single from Everth Cabrera. Chase Headley singled in another run for the 4-2 lead.
San Diego starter Eric Stults gave up a two-run home run to Scott Hairston in the seventh. He was pulled later in the inning and Joe Thatcher (2-0) got the final out of the inning the ended up with the win. Huston Street allowed a double and had a strike out in picking up his sixth save.