Downs also added a single while J.D. Martinez picked up two hits and a run scored and Jason Bourgeois added a pair of hits for Houston, which has won back-to-back games.
David Carpenter (1-3) earned the win, throwing a third of an inning in relief, while Mark Melancon worked a 1-2-3 ninth to earn his 19th save of the year.
"When he's not starting, he does a good job of getting himself ready," Astros manager Brad Mills said of Downs. "When he does start, whether it's second, third, first or the outfield, when you have a guy like that, that puts up the production he does, it's extremely valuable."
Brandon Phillips smacked a solo home run and Todd Frazier laced an RBI double for the Reds, losers in four straight games.
The Astros plated two runs in the sixth to tie the game. Martinez singled off Ondrusek and Carlos Lee walked before Downs slapped a ball down to third that Frazier couldn't handle, allowing Martinez to score. Jimmy Paredes then reached on a bunt single and Clint Barmes rocketed one to third, which Frazier made a nice diving stop on and got a force-out at second, but Lee crossed the plate on the play.
Houston put two runners on in the seventh against Jose Arredondo, but were unable to take the lead, as Lee grounded into a fielder's choice to keep the game tied.
The Reds threatened in the home half, putting the go-ahead run at second with two outs and Phillips at the plate, but he hit a weak ground ball to shortstop on a 3-0 count to end the inning.
"We made some mistakes tonight," Reds manager Dusty Baker said. "We missed some signs, we missed a squeeze, we missed a 3-0 swing, and we hit the ball on the ground into double plays at the wrong time."
Cincinnati wasted no time opening the scoring in its first at-bat when Phillips drove a high fastball from J.A. Happ three rows deep into the seats in right-center field.
The Reds added a run in their next at-bat when Drew Stubbs worked a walk, stole second and came around to score on a double down the left field line by Frazier.
Ramon Hernandez singled up the middle to begin the Reds fifth and moved to second on a well-placed sacrifice bunt by starter Travis Wood. Phillips then walked to put two runners on. Cincinnati was unable to cash in however, as Edgar Renteria grounded into a 5-3 double play.
Reds manager Dusty Baker is one win shy of 1,480 for his career, tying him with Hall of Famer Earl Weaver for 21st on that all-time list...Reds starting pitcher Mike Leake was used as a pinch runner in the seventh inning...It was Downs' ninth homer of the season...Wood scattered four hits over five scoreless innings while fanning two and walking two...Happ gave up two runs on three hits while striking out a season-high nine batters and walking three over six frames.