The Padres were clinging to a one-run lead when Chris Denorfia opened the eighth with a single. Venable then hit a 1-0 pitch from Heath Bell out to right and two outs later Guzman delivered a solo shot.
San Diego salvaged the finale of the three-game series.
Venable's double and Guzman's single also produced the first two San Diego runs in the opening inning, setting up starter Robbie Erlin for the win.
Erlin (2-2) allowed a run on six hits in six innings. Arizona managed its one run on 10 hits and left 11 men on base.
The two first-inning San Diego runs were the only ones allowed by Wade Miley (9-9), who gave up seven hits in seven innings to take the loss.