Castillo had loaded the bases on singles by Franmil Reyes and Freddy Galvis, and a walk to Manuel Margot. Reyes was forced at home on Raffy Lopez’s dribbler before Renfroe’s slam.
Lopez hit an RBI single in the sixth.
Ross (5-3) gave up two runs and seven hits in five innings, struck out three and walked two. He’s won three straight decisions, over four starts.
He allowed Eugenio Suarez’s leadoff homer to left in the second, his 11th, and Scooter Gennett’s RBI single in the fifth.
With the Padres leading 5-2, manager Andy Green had closer Brad Hand face the heart of the Reds’ order in the eighth, including lefty-hitting Joey Votto and Gennett. Votto, who had three hits, struck out, but Hand then allowed a homer to Gennett, his 12th. Suarez struck out, Adam Duvall singled and Jose Peraza flied out.
Cory Spangenberg homered for San Diego in the eighth, his fourth.
Kirby Yates pitched the ninth for his first save. Votto came up with two on and two outs and grounded out to end it.
Castillo (4-6) allowed four runs and six hits in 4 2-3 innings, struck out three and walked one.
The Reds return home and open a three-game series Tuesday night vs. the Colorado Rockies.