Keselowski had earned the pole in his previous two races but hadn't won.
It was a good overall day for Keselowski, who earlier in the day qualified fifth for today's Brickyard 400.
James Buescher finished second. Polesitter Ricky Stenhouse Jr. led 189 laps before finishing third. He led by nearly four seconds in lap 175 before the field tightened because of a caution following an accident.
Stenhouse still moved ahead of Reed Sorenson into the points lead. Sorenson finished ninth.
Elliott Sadler crashed out on lap 198 while battling Keselowski and Stenhouse for the lead, bringing out a caution and setting up the shootout to the finish. Sadler's crash allowed Keselowski to move up to the front row with Stenhouse, and Keselowski took advantage of his short-run speed to win.
Action sports star Travis Pastrana was supposed to race on Saturday, but he fell at the X Games on Thursday night and broke his right foot and ankle.
NASCAR has announced that the race will move to Indianapolis Motor Speedway next year after 30 years at Lucas Oil Raceway.
RIVALRY RENEWED: Roger Penske has 15 victories as a car owner in the Indianapolis 500. Chip Ganassi has three. Ganassi, however, has something Penske doesn't -- a Brickyard 400 win.
Penske and Ganassi are the most formidable car owners in the IndyCar Series. Together they've combined to win the past five IndyCar championships, but neither has won a NASCAR title.
Their drivers hope to change all that, starting with today's stock car race at Indianapolis.
"Roger is always excited about Indianapolis," Kurt Busch said of his boss. "The race team, everybody is just amps it up. Of course I want to win here at Indianapolis. To deliver that first (Indy) trophy on the Cup side is the optimum goal -- to do that for Roger Penske here at Indianapolis."
Jamie McMurray gave Ganassi bragging rights a year ago by winning the Brickyard 400. Juan Pablo Montoya gave Ganassi his first Indianapolis 500 win in 2000. Both are in today's race.
FORMULA ONE: In Budapest, Hungary, Sebastian Vettel reminded his Formula One rivals that Red Bull remains the team to beat in the championship after taking the pole position for the Hungarian Grand Prix.
The F1 leader's crew worked on his car through the night, and he earned a leading time of 1 minute, 19.815 seconds Saturday on his last lap.
McLaren took advantage of mixed weather conditions to qualify second and third. Lewis Hamilton was within two-tenths of the German leader and finished in front of teammate Jenson Button. Ferrari pair Felipe Massa and Fernando Alonso followed, while Mark Webber will start sixth for Red Bull.