Scott Hairston, whose two-run homer beat the Astros on Tuesday, was once again Houston's nemesis as he reached base four straight times with a walk, single, double and triple.
It was his triple to center field with one out in the seventh that set up the go-ahead run. With the score tied at 2, Hairston came home when Tadahito Iguchi lined a single through a drawn-in infield.
Enrique Gonzalez (1-0), who gave up the tying run in the top of the seventh, got the victory.
Trevor Hoffman, who suffered a blown save Wednesday night, came back and hurled a perfect ninth and picked up his second save of the season and 526th of his career.
Starting pitchers Randy Wolf and Chacon pitched well in their respective debuts for their new clubs, both pitching six innings.
Wolf allowed one run on four hits. He walked two and struck out five. He threw 103 pitches with 71 for strikes. The lone run he allowed came in the third inning on an RBI double by Mark Loretta which scored Hunter Pence from first base.
Chacon allowed two runs on five hits in his six innings of work. He walked four and struck out four and gave up one home run, a two-run shot to San Diego's Kevin Kouzmanoff in the first inning. He loaded the bases in the second inning with two straight walks before getting Adrian Gonzalez on a tapper back to the mound.
"The first and second innings, I let things get away from me a little bit," said Chacon, who was signed by the Astros as a free agent on Feb. 20.
"I was able to find a groove and finish strong," said Chacon, who limited the Padres to just two hits over his final four innings.
As for the home-run pitch to Kouzmanoff, it came on the first pitch.
"It was a fastball that hung out over the plate," said Chacon. "He put a good swing on a ball that was up and he did what he's supposed to do. Looking back, it wasn't a pitch that I wanted to throw. But that was a mistake, but sometimes you have to tip your hat.
"You want to come out and try and be aggressive. There were two outs and I don't know how often guys are going to come out hacking at that first pitch. But it still wasn't a quality pitch."
Hairston had opened the first with a double to shallow left field. Chacon struck out Iguchi and got Gonzalez to fly to left with Hairston moving over to third.
"I thought there were some command issues at times," said Cooper, "but for the most part [Chacon] was really good today."
The Astros tied the game at 2 in the top of the seventh on an RBI double by catcher J.R. Towles. Jose Cruz Jr., who had walked with one out, came around to score on Towles' drive that went into the left-field corner, similar to Loretta's drive back in the third.
Heath Bell tossed a scoreless eighth inning for the Padres before Hoffman came in in the ninth.
"Obviously, you're not going to get to Hoffy very often, we were fortunate last night," said Cooper. "But today was pretty easy going. With both he and Bell, they are two of the best in the business.
"You have to give plenty of credit to Wolfie. He gave them six solid innings," said Cooper. "We were chasing some pitches out of the zone and once again, we just couldn't get the hit with runners in scoring position."
Coming into Thursday's game the Astros were 2-for-22 with RISP and went 0-for-7 on Thursday.