Rodriguez (14-11) allowed two runs and nine hits. He struck out nine and walked one in his career-high 32nd start of the season.
"I felt great," said Rodriguez, who also has set career bests in wins, strikeouts (190) and innings (199 2/3) this season. "Everything was working good for me. My breaking ball was really good. I didn't think they could hit my breaking ball today."
Houston improved to 2-4 under interim manager Dave Clark, who was impressed with Rodriguez's crisp effort. The Astros had lost nine straight against the Reds.
"Wandy had a good breaking ball today," said Clark, who took over for Cecil Cooper last Monday. "He also had good command of his fastball. When you see him go to his breaking ball too often, that's when he has problems. But he was able to mix it up today."
Jeff Fulchino worked a perfect seventh, LaTroy Hawkins threw a scoreless eighth and Jose Valverde finished up for his 25th save. Valverde has converted 19 straight save opportunities and hasn't allowed a run in his last 12.
Reds starter Johnny Cueto (10-11) went 7 1/3 innings, giving up three runs and six hits. He struck out five and walked five.
"Johnny pitched outstanding," manager Dusty Baker said. "His pitch count wasn't that high, as long as he went. He just had that one inning where he lost control of the strike zone and they scored on a couple of fielder's choices."
The Reds had scored 10 runs apiece in each of the first two games of the series.
"I felt good and I was really locating my pitches well today," Cueto said. "The hitters have a job to do and I have a job to do. I can't tell them to hit. They scored a lot of runs the last two games. There's nothing I can do about it."
Quintero hit his fourth homer of the season in the fourth.
Miguel Tejada's seventh-inning double for Houston gave him a 14-game hitting streak, the longest active string in the NL. ... Cincinnati 3B Scott Rolen missed his third straight game with back spasms. ... Astros 2B Kaz Matsui was out of the starting lineup due to flulike symptoms. Edwin Maysonet took his place, but Matsui entered on defense in the ninth.