Keselowski put on a dominating performance by leading 158 of 200 laps and crossing the finish line 8.6 seconds ahead of fellow Sprint Cup Series competitor Carl Edwards for his third win of the season and the 15th of his Nationwide career.
His Nationwide win comes on the eve of the first race in the Chase for the Sprint Cup championship. He made the playoffs in NASCAR's premier series for the first time, earning a wild card spot with his three Sprint Cup victories.
"It's a great boost to get a win before going into the Chase," Keselowski said.
Keselowski, the 2010 Nationwide champion, claimed his first win in the series since he suffered a broken left ankle and a sore back in a crash while testing the first week in August at Road Atlanta.
Edwards took the top position from Keselowski on lap 90 and then held a sizeable lead. But Edwards experienced a fuel issue shortly after, which held him up in the pits during a mid-race round of stops and cost him an opportunity to win.
"[The car] started to stumble a little bit, and I said, 'It's out of fuel, it's out of fuel'," said Edwards, who led 35 laps. "The guys did a really good job of putting fuel in it. We did lose some time."
Edwards, who's also in the Chase, and Keselowski will start Sunday's 400-mile Sprint Cup race from the third row.
Sadler trimmed Stenhouse's points lead to 14 with just six races remaining this season.
"We struggled all day, and there's no reason why we shouldn't run in the top- five every week," Stenhouse said. "We'll go to work. I think we just missed it in practice."
Sorenson is now 47 points behind Stenhouse.