The Dodgers prospect allowed two hits and did not walk a batter over 6 2/3 dominant innings to win for the second time in four starts.
"I don't really try to strike out a lot of people, just try to get outs, so obviously, I feel great," said Santiago, a 2007 16th-round Draft pick. "This is the first time I've struck out that many guys. Once I got to two strikes, I was just able to finish them off. It's really great I had so many."
Santiago gave up a one-out single to Padres No. 6 prospect Cory Spangenberg in the first inning, then retired 17 batters in a row until Spangenberg led off the seventh with another base hit.
In his fifth season out of Puerto Rico's Colegio Carmen Sol, Santiago (2-1) lowered his ERA to 2.22, which ranks eighth in the hitter-friendly California League. He's also averaging 10.7 strikeouts per nine innings.
The 22-year-old right-hander said his changeup and the ability to throw it for strikes, has been a key over his last few outings.
"My changeup is the out pitch. I like to throw it with two strikes," he said. "I actually struck out a couple guys today with my slider, but my best pitch after the fastball is my changeup. If I can throw it for a strike, it's a strikeout pitch."
Santiago is back in the Cal League after spending all of last season with the Quakes. He was 8-5 with a 5.03 ERA over 121 2/3 innings in 28 appearances, including 20 starts.
Santiago has worked this season with pitching coach and former Major Leaguer Matt Herges on refining his off-speed offerings, particularly the changeup and slider. The hope is that he will be able to duplicate the success he enjoyed Sunday.
"I want to try to be aggressive with my fastball, but I wasn't giving hitters too much credit if they weren't hitting it," he said. "I would repeat it and then I wouldn't throw it for misses. I can be successful with that with the changeup, I'm feeling pretty comfortable with it."
Scott McGough followed Santiago and allowed one hit in 1 1/3 scoreless innings before Logan Bawcom struck out all three batters he faced in the ninth. They finished off the Quakes' second shutout of the year.
Austin Gallagher went 3-for-5 with a double and three RBIs, while Chris Jacobs also collected three hits for Rancho Cucamonga. The Quakes struck for two runs on six hits over 3 2/3 innings against Padres right-hander Tim Stauffer, who made a rehab start for the Storm.