Bowyer dominated the race after he slipped by Dario Franchitti for the lead on lap 107, but appeared to wiggle exiting the second turn on the 227th lap as Keselowski went past him.
"We were dead equal, Clint and I," Keselowski said after climbing from his car in the cloud of smoke of a just-completed burnout. "I needed to catch a break and he gave it to me."
Car owner Dale Earnhardt Jr. greeted Keselowski after the finish.
"Victory Lane, Bristol," the boss told his driver. "It gets no better than that, man."
Bowyer, who has won just once, was dejected after leading 121 laps.
"It was good right up until whatever lap that was where I made a mistake," he said, adding that he tried too quickly to get back on the gas coming out of the second turn. "It came out from underneath me there and I had to check up or I would have spun out."
Bowyer quickly gathered his car and gave chase, but Keselowski held on, moving him closer to Bowyer atop the points standings after 29 of 35 races. Keselowski is now 122 points behind Bowyer, and Carl Edwards dropped to third.
Bowyer held on to finish second, followed by Greg Biffle, pole-sitter Cale Gale and David Stremme in a race that was slowed just five times by cautions, and for only 26 laps.
Bowyer has finished in the top 10 in 21 of 26 races, but with just one win.
"It's been a frustrating two months for me," Bowyer said. "It's good when you can be frustrated with second, but we did give one away today. When you look at it, it was obvious."
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