It was the 1,000th victory for Ford across NASCAR's three national series -- Cup, Nationwide and Truck.
It was Biffle's first win since he overtook Johnson to win at MIS in August. Johnson's engine faltered with six laps left in that race. This time, he was about a second behind Biffle with three laps to go -- but a tire give way, and he dropped all the way to 28th.
"We beat (Johnson's) 48 today and that says a lot. He was really, really fast," Biffle said. "Once we got out in clean air, we could match up fairly well with the 48. He made a small mistake trying to catch us."
Harvick was second, 3 seconds behind Biffle. Martin Truex Jr. was next, followed by Kyle Busch and Tony Stewart.
Johnson wasn't the only big name who ran into trouble. Jeff Gordon was out of contention when he hit a spinning Bobby Labonte less than 10 laps into the 200-lap, 400-mile race. Gordon finished 39th, one spot behind Kasey Kahne, who led at the halfway point but appeared to blow a tire and went sliding into the wall.
Kahne's car caught fire, but he was able to climb out quickly.
Dale Earnhardt Jr., who won at MIS last June, finished 37th Sunday. He led for 34 laps, but his engine acted up about two-thirds of the way through the race.
There were eight cautions for 38 laps.
Pole winner Carl Edwards finished eighth. Kurt Busch qualified second but went into an early spin and finished 35th.
Biffle earned his 19th career victory and boosted his chances to reach the Chase for the Sprint Cup. He was 10th in the standings entering the day.
Biffle finished in the top 10 for the 13th time in 21 races at MIS.
Johnson still has a comfortable lead in standings, although Edwards closed the gap at the top from 51 points to 31. Johnson had a chance at his fourth victory of the year before scraping the wall late.
Johnson has still never won a Cup race at MIS.
"I thought this would be the year," he said. "Most of the time we're leading and something happens, but I thought, `OK, maybe coming from behind would be the difference.' But something happened."
Biffle cruised to the finish line in his No. 16 Ford. He finished second to Johnson last weekend at Pocono, but this time there was nobody left to challenge him at the end.
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