The 44-year-old Colon was working on a perfect game for the Texas Rangers before walking Carlos Correa on a 3-1 pitch to start the eighth. Reddick then lined an 0-2 delivery down the right-field line, putting runners at second and third.
Opposing fans in Houston gave Colon a standing ovation, and he clapped his bare hand softly against the outside of his glove.
Two outs later, Colon was removed with the score tied at 1. He struck out seven and ended up with a no-decision.
On his way from the mound to the dugout, the good-humored Colon gestured toward Reddick with a quick flick of his hand.
Colon threw 96 pitches, 66 for strikes. A fan favorite all around the majors, the beefy right-hander nicknamed "Big Sexy" is on his ninth team in his last 11 seasons.
Colon's longest no-hit bid came with the Cleveland Indians on Sept. 18, 2000, when he held the New York Yankees hitless for 7 1/3 innings. He finished with a one-hitter in a 2-0 win at Yankee Stadium.
Going into the eighth, Texas led 1-0 on a home run by Robinson Chirinos off Astros ace Justin Verlander in the third, the only hit of the game to that point.
In the dugout, Colon's teammates left him all alone on the bench - adhering to traditional superstition - as he grinned and tossed a ball to himself.
Kenny Rogers threw Texas' most recent no-hitter, in July 1994.
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