He followed last week's victory in the Coca-Cola 600 with another sensational run in a race red-flagged for 22 minutes because of a pothole in the concrete track.
Johnson led 272 of 400 laps, and won consecutive races for the 13th time. The six-time Cup champion swept Dover in 2002 and 2009 and won races in 2005, 2010, 2012 and 2013.
Brad Keselowski was second, followed by Matt Kenseth, Clint Bowyer and Denny Hamlin.
"For sure, when you come to Dover, it's always the 48," Kenseth said. "We've got to figure out how to get ahead of him."
Johnson also became Dover's career leader in laps led when he hit the 2,802 mark.
"It's incredible," Johnson said. "So much to be thankful for."
Johnson never left any doubt his No. 48 Chevrolet was the car to beat, the only drama coming when the race was stopped 160 laps into the race after Ryan Newman's car pulled up chunks of the track that kicked back and damaged Jamie McMurray's car. The race was soon stopped and crews weren't allowed to work on the cars.
McMurray's plea for an exception was denied.
More pieces of the track flew up and cracked a window on the pedestrian crossover bridge.
NASCAR officials and safety crews went to work on the potholes and applied a quick-drying concrete mix. Cup races were infamously delayed by potholes at Martinsville in 2004 and the 2010 Daytona 500. McMurray won at Daytona in 2010.
"You knew it was going to get worse if someone didn't repair it," Keselowski said. "I thought the repair was pretty good. You could feel it a little bit."
Kevin Harvick might have wished for a longer delay. Harvick's lead at the red flag evaporated because of a flat tire not long after racing resumed and he fell two laps behind Johnson. Harvick worked his way back into a 17th-place finish.
Kyle Busch led the first 81 laps before Johnson passed him. Busch's bid for a tripleheader sweep at Dover would soon end when the No. 18 Toyota slammed into the outside wall. Bowyer moved into Busch's line, which caused him to wreck 124 laps into the race.
Busch won the Truck Series race Friday and the Nationwide race Saturday. He has the only three-race sweep since NASCAR expanded to three national series in 1995, accomplishing the feat in 2010 at Bristol.
Busch, who did not talk to the media, is 1 for 9 in Cup races after winning the first two in the same weekend.
Busch had some company in the garage. AJ Allmendinger turned into Greg Biffle and Ricky Stenhouse Jr. on Lap 135, which knocked out the Roush Fenway Racing teammates. Biffle, though, later returned to finish.
"They were racing hard back there and he stuck it into a hole that maybe there wasn't room for," Biffle said.