But things got wild in the fifth and it ended up costing the Padres.
J.D. Martinez hit a two-run homer, Jed Lowrie added a solo shot and the Astros held on for a 5-3 win.
Wells (0-1) became the 13th different starter in San Diego's revolving-door rotation by making his first major league appearance since 2009. Signed to a minor league deal May 7, Wells yielded seven hits and five runs—two earned—in five innings.
"In general, I feel like I didn't really change my agenda or pitch selection or my effort level even in the last inning," Wells said. "At times, you have a tendency, at least for me, when the pressure gets on and guys in scoring position, to try to do more and that can backfire on you more than you think because you tend to leave pitches up."
San Diego manager Bud Black said Wells' stuff was pretty good, but he was a bit erratic at times.
"His fastball had some movement to it," Black said. "He had some arm-side sink. When it was down in the zone, it stayed pretty true. Other times it would cut. He had a good hard slider and worked a couple of curveballs."
The 35-year-old Wells hadn't pitched in the majors since Oct. 1, 2009, when he allowed five runs in two-plus innings of a 13-0 loss to St. Louis with the Reds. He was
Lowrie started the fifth with a single and went to third on an error by Wells, who overthrew second base on Brian Bogusevic's one-out comebacker.
The Astros took a 2-1 lead when Lowrie scored on a wild pitch before Chris Johnson's run-scoring single, which extended his hitting streak to seven games.
Then came Martinez's 10th home run of the season to push Houston's lead to 5-1.
"Obviously, from an individual standpoint, you see that you shot yourself in the foot a little bit," Wells said about the error. "The home run that Martinez hit, the pitch was a decent pitch. It was down and middle in. It wasn't just a cookie, but I would have liked to have not cashed myself in for more runs."
Houston starter Jordan Lyles (2-4) allowed six hits and a run in 6 1-3 innings to break a three-game losing streak and earn his first victory since June 3.
The game was tied at 1 after Will Venable and Lowrie exchanged solo homers in the third.
Venable hit a ball that bounced off the top of the wall in right field and back onto the field for what was first called a triple to start the inning. The play was reviewed and Venable had his sixth homer to put San Diego up 1-0.
Lowrie evened things up with his team-leading 14th home run to start the Houston third. The ball dropped into the Astros bullpen in right-center, where reliever David Carpenter had to scramble to avoid being hit by it.
Wells said he tried to be a little more aggressive after Lowrie's home run.
"I can't really say that I kick myself a whole lot for most of the pitches other than the fielding error on my part, which was unfortunate," Wells said. "For the most part, I feel like I kept the ball down. I didn't get away too much from sinkers."
That wasn't the only action of the night for Carpenter, who allowed a single and a walk before being replaced by closer Brett Myers with one out in the ninth. Chase Headley's two-run single with two outs got San Diego within 5-3.
John Baker's single sent Headley to third before Myers plunked Everth Cabrera to load the bases. Myers escaped the jam and got his 17th save when Alexi Amarista grounded into a force out.
"It was a spirited rally," Black said. "We had the bases loaded. We had the winning run on first base. We were down four runs in the ninth with Myers in the 'pen and we get it to bases loaded with the winning run at first. Alexi hit the ball on the nose, just not out of the range of the shortstop. Good comeback."
Houston's offense has come alive in the last four games, piling up 10 homers and 27 runs, after scoring just one run in the previous three games combined.
Lyles got into trouble in the second when Baker reached on an error by Johnson with one out before consecutive singles by Cabrera and Amarista loaded the bases. But Lyles retired the next two batters to work out of the jam.
NOTES: The Padres began wearing patches with No. 48 on their uniforms in honor of longtime bullpen coach Darrel Akerfelds, who died of pancreatic cancer on Sunday. ... The Padres recalled Nick Vincent from Double-A San Antonio and optioned INF Andy Parrino and RHP Brad Boxberger to Tucson. They also moved RHP Joe Wieland (strained right elbow) from the 15-day disabled list to the 60-day DL. ... ... The Padres signed OF Travis Jankowski, the 44th pick in this year's amateur draft, and 11th-round pick INF Maxx Tissenbaum.