Although Johnson was the driver to beat for most of the day, leading a race-high 157 laps, his Penske rival surged on the penultimate restart to grab the lead as the reigning champion spun his tyres while powering off under the green flag.
Busch made the most of his rival's mistake to take the lead and never look back as Johnson started getting pressure from a charging Carl Edwards, who recovered from a pit-road penalty. In the end the Penske driver was able to manage a further restart and then traffic, keeping a gap at the front while Johnson did enough to keep Edwards in his mirrors.
The 2004 Cup champion had led the race early on but as the track rubbered in he seemed to lose pace relative to his rivals. The right adjustments and good strategy calls enabled him to get back in contention for a victory that seemed unlikely at first given Johnson's dominance.
Busch's second win of the season means he jumps up in the Chase standings to fourth place, as the play-off ranking was shaken following a bad day for previous leader Tony Stewart, who struggled throughout the weekend and finished two laps down in 25th.
"I just wanted to get out in front of [Jimmie] Johnson," said Busch about the decisive restart on lap 359 out of 400. "The first restart, I was on the high side. I didn't know what to choose, low or high.
"I just wanted to get that jump on him and stretch our lead because I thought that he would reel us back in with about 10 to go. We just had to maintain and bring our Dodge Charger to victory lane."
Johnson had looked dominant on the long green-flag runs but that speed didn't transpire in the final stint of the race while in dirty air behind Busch. The reigning champion lamented letting a possible win slip away but his second-place finish enabled him to get back in the thick of the title battle, moving up five spots in the Chase ranking.
"I blew it by spinning the tyres," Johnson said. "Kurt got a good launch, and we were door to door going into one, and he was able to get by on the outside.
"And then the next [restart], I was going to try to do that same thing back to him, and I was just trying to time when he was going to accelerate. I didn't time it right, had too big of a gap, and fell in behind him going into turn one."
Roush Fenway's Edwards could have also been a threat for victory had he not been forced to come back from a lap down following his pit-road penalty. He crossed the finish-line right behind Johnson and grabbed enough points to join Kevin Harvick in the lead of the play-off.
"That's the first time I've been caught speeding on pit road all year, but I've done it like 15 times in the Nationwide Series," said a frustrated Edwards.
Red Bull's Kasey Kahne gave his team some hope with a solid run to fourth-place, looking like a victory contender at stages but having his charge for the lead cut by one of the caution periods in the second half of the race.
Edwards' team-mate Kenseth was a top-five contender for most of the day but lost track position after his final stop, taking four tyres while most of the leaders took only two. He moved up from ninth to fifth in the closing laps and remains seventh in the championship.
Joe Gibbs Racing's Kyle Busch was sixth but lost two places in the Chase standing, while AJ Allmendinger and Marcos Ambrose rounded a good day for Richard Petty Motorsports with seventh and ninth respectively, split by Richard Childress Racing's Clint Bowyer.
Harvick now shares the Chase lead with Edwards, while Stewart's tough weekend means he drops to third, now nine points behind in the title race. It was a rough day for the Stewart-Haas organization as a whole, as Ryan Newman also finished two laps down in 23rd. Neither car had the speed to run close to the top-ten all day.
Hendrick Motorsports' Jeff Gordon was 12th and has dropped in the standing as well, while his team-mate Dale Earnhardt Jr had to pit under green for a suspected loose wheel late in the race and was unable to get back on the lead lap finishing in the middle of the two Stewart-Haas drivers.
Penske's Brad Keselowski ran out of sequence at one stage while trying to make up ground following a power-steering issue that dropped him out of the lead lap. Although he was able to get back in it, he wouldn't make further progress and crossed the finish-line 20th.
Results - 400 laps: Pos Driver Team/Car Time/Gap 1. Kurt Busch Penske Dodge 3h30m59.908s 2. Jimmie Johnson Hendrick Chevrolet + 0.908s 3. Carl Edwards Roush Fenway Ford + 1.149s 4. Kasey Kahne Red Bull Toyota + 3.744s 5. Matt Kenseth Roush Fenway Ford + 5.450s 6. Kyle Busch Gibbs Toyota + 7.855s 7. AJ Allmendinger Petty Ford + 8.344s 8. Clint Bowyer Childress Chevrolet + 9.858s 9. Marcos Ambrose Petty Ford + 11.310s 10. Kevin Harvick Childress Chevrolet + 11.873s 11. Jeff Burton Childress Chevrolet + 12.207s 12. Jeff Gordon Hendrick Chevrolet + 12.392s 13. David Reutimann Waltrip Toyota + 13.069s 14. Brian Vickers Red Bull Toyota + 14.425s 15. Jamie McMurray Earnhardt Ganassi Chevrolet + 15.205s 16. Paul Menard Childress Chevrolet + 15.353s 17. Regan Smith Furniture Row Chevrolet + 15.510s 18. Denny Hamlin Gibbs Toyota + 16.035s 19. Mark Martin Hendrick Chevrolet + 16.358s 20. Brad Keselowski Penske Dodge + 16.951s 21. David Ragan Roush Fenway Ford + 1 lap 22. Juan Pablo Montoya Earnhardt Ganassi Chevrolet + 2 laps 23. Ryan Newman Stewart Haas Chevrolet + 2 laps 24. Dale Earnhardt Jr Hendrick Chevrolet + 2 laps 25. Tony Stewart Stewart Haas Chevrolet + 2 laps 26. Bobby Labonte JTG Daugherty Toyota + 2 laps 27. Greg Biffle Roush Fenway Ford + 3 laps 28. David Gilliland Front Row Ford + 3 laps 29. Joey Logano Gibbs Toyota + 3 laps 30. Martin Truex Jr Waltrip Toyota + 4 laps 31. Landon Cassill Phoenix Chevrolet + 5 laps 32. Dave Blaney Baldwin Chevrolet + 5 laps 33. Andy Lally TRG Chevrolet + 6 laps 34. JJ Yeley Front Row Ford + 10 laps 35. Casey Mears Germain Toyota + 34 laps 36. Mike Bliss FAS Lane Ford + 54 laps Retirements: Josh Wise Max Q Ford 56 laps Reed Sorenson Gordon Dodge 52 laps Joe Nemechek NEMCO Toyota 49 laps Michael McDowell HP Toyota 44 laps David Stremme Inception Chevrolet 31 laps Scott Speed Whitney Ford 24 laps Travis Kvapil Front Row Ford 12 laps