After Patrick led the field of 43 cars to the green flag for the start, Jeff Gordon, who began second, pulled ahead of her and then ran in front for the first 31 laps. Patrick led her first of five laps in this race after a restart on lap 90.
Mark Martin finished third, while Keselowski settled for fourth. Ryan Newman was fifth.
Greg Biffle placed sixth and Regan Smith seventh. Michael McDowell and J.J. Yeley completed the top-10.
After crossing the start/finish line to complete the penultimate lap, Travis Kvapil made contact with the outside wall. NASCAR officials did not display the yellow flag on the final lap, which would have ended the race under caution.
Despite two big wrecks involving nine drivers in each one of them, the Daytona 500 settled nerves after Saturday's horrifying accident in the Nationwide Series race at this 2.5-mile racetrack.
At least 28 spectators were injured, two of them critically, when debris from Kyle Larson's car stuck them in the grandstands along the frontstretch. Larson, a rookie in Nationwide this year, flipped around and sailed into the catchfence in the tri-oval area after he was caught up in a 12-car crash. The front end of his vehicle ripped apart when it tore a gaping hole in the fence.
The Daytona 500 started at its scheduled time, as track personnel feverishly worked on the fence overnight to repair it.
On lap 34, Tony Stewart and Kevin Harvick had their chances of winning the Daytona 500 come to an abrupt end when they were involved in the first nine- car wreck. Kyle Busch hit Kasey Kahne and spun him around, which triggered the incident. Keselowski sustained slight damage to the front end of his Ford.
Stewart spent more than 80 laps in the garage area for repairs before returning to the track to finish the race in 41st. The three-time series champion has yet to win the Daytona 500 in 15 attempts.
"I wanted to win the Daytona 500," he said. "I don't know what started it, but we just got caught up in another wreck."
Harvick, the 2007 race winner, finished one spot behind Stewart in 42nd. He won the Sprint Cup preseason race at Daytona eight days ago and scored a victory in the first event of Thursday's twin-qualifiers.
"I let off a little bit to miss the wreck," Harvick said. "I don't know who was behind me, but it was just one of those deals."
Carl Edwards was involved in the second multi-car wreck of the day. Edwards had a miserable Speedweeks at Daytona, crashing in two separate practice sessions and in the qualifiers four days ago. He also wrecked in testing here last month.
"This is so frustrating," Edwards said. "It's not been fun."
Matt Kenseth appeared to be on the way to his second consecutive and third overall win in the Daytona 500 until he suffered engine failure with 50 laps remaining. Kenseth, who is in his first year with Joe Gibbs Racing after spending the past 13 seasons with Roush Fenway Racing, led a race-high 86 laps. He finished 37th.
"We were one of the cars to beat today, and I think we're going to be a force all year, so we have a lot to look forward to," Kenseth said.
His JGR teammate, Busch, suffered engine problems and retired from race the two laps after Kenseth called it a day. Busch placed 34th.