The Joe Gibbs Racing driver started from pole position, led the most laps but had to defend his lead on the final two-lap sprint against Johnson. Although the Hendrick driver was initially able to keep the pressure on, he then came under attack from a charging David Reutimann (Michael Waltrip Racing), allowing Busch to pull ahead to his third win of the season.
Busch had also won Thursday's Truck Series race, which meant Saturday's victory places him only one shy of his 100th NASCAR win.
"This is right up there with the best of them. I haven't won the big ones but this is as good as it gets, man. The way we won was awesome," said Busch, who has jumped up to the top of the standings and has all but locked up a place in this year's Chase.
Track position and running in clean air proved crucial on the bumpy Kentucky asphalt, and although Busch was ahead of the field for longer than his rivals, Penske's Brad Keselowski proved to be a threat after he took the lead for the first time on lap 142 having stayed out during the second caution of the day.
Keselowski, winner of Saturday's Nationwide Series race, led 79 laps but lost a couple of seconds at his final planned stop for fuel under green with 27 laps remaining. That probably cost him the chance to put up a tougher fight for victory in the end, eventually crossing the finish line in seventh.
"At the end, the restarts are just a crapshoot," said Keselowski. "If you get the bottom lane, you're going backwards. I kept getting in an odd position and just kept getting on the bottom lane. Every restart just kept playing against us. A great effort by this race team and that makes me proud. We led laps and were competitive all night."
His team-mate Kurt Busch also led a good portion of the race but finished only ninth in the end.
Reutimann got a lucky break when the fifth caution of the day waved as everyone but him had completed their final scheduled stops for fuel. When Dale Earnhardt Jr blew a left-front tyre after stopping for fuel, only seven cars were on the lead lap, which meant the Michael Waltrip Racing driver was able to stop under caution and drop only a handful of spots.
Johnson was a top-five contender for most of the evening and his second place in the end allowed him to move up a spot in the points to fifth place. Stewart Haas' Ryan Newman recovered from being a lap down to finish fourth behind Johnson after a bold final restart.
Roush Fenway's Carl Edwards rounded out the top five ahead of his team-mate Matt Kenseth, while last week's Daytona winner David Ragan continued to move up in the standings with an eighth place finish.
Tony Stewart was a top five contender but in the end he had to make do with 12th while similarly Earnhardt Ganassi's Juan Pablo Montoya was only 15th after being sent to the rear of the field for the penultimate restart while he was running seventh, following a penalty for speeding in the pits. The Colombian had been a contender for a solid finish before that.
Former points leader Kevin Harvick struggled to a 16th place finish and dropped down to third in the standings.
The inaugural Cup event at Kentucky proved a success in terms of attendance as numbers reportedly exceeded the 106,000 grandstand capacity, although such crowds made for massive traffic issues both before and after the event, with some fans even being unable to reach the track.
Results - 267 laps: Pos Driver Team/Car Time/Gap 1. Kyle Busch Gibbs Toyota 2h55m00.000s 2. David Reutimann Waltrip Toyota + 0.179s 3. Jimmie Johnson Hendrick Chevrolet + 0.233s 4. Ryan Newman Stewart Haas Chevrolet + 0.887s 5. Carl Edwards Roush Fenway Ford + 1.158s 6. Matt Kenseth Roush Fenway Ford + 1.398s 7. Brad Keselowski Penske Dodge + 1.506s 8. David Ragan Roush Fenway Ford + 1.544s 9. Kurt Busch Penske Dodge + 1.576s 10. Jeff Gordon Hendrick Chevrolet + 1.971s 11. Denny Hamlin Gibbs Toyota + 1.972s 12. Tony Stewart Stewart Haas Chevrolet + 2.270s 13. Kasey Kahne Red Bull Toyota + 2.374s 14. Joey Logano Gibbs Toyota + 2.702s 15. Juan Pablo Montoya Earnhardt Ganassi Chevrolet + 2.737s 16. Kevin Harvick Childress Chevrolet + 2.852s 17. Regan Smith Furniture Row Chevrolet + 3.069s 18. Martin Truex Jr Waltrip Toyota + 3.380s 19. Jeff Burton Childress Chevrolet + 3.496s 20. Marcos Ambrose Petty Ford + 3.544s 21. Greg Biffle Roush Fenway Ford + 3.682s 22. Mark Martin Hendrick Chevrolet + 3.962s 23. Landon Cassill Phoenix Chevrolet + 6.157s 24. Paul Menard Childress Chevrolet + 1 lap 25. Casey Mears Germain Toyota + 1 lap 26. Bobby Labonte JTG Daugherty Toyota + 1 lap 27. Brian Vickers Red Bull Toyota + 2 laps 28. AJ Allmendinger Petty Ford + 2 laps 29. Travis Kvapil Front Row Ford + 2 laps 30. Dale Earnhardt Jr Hendrick Chevrolet + 2 laps 31. David Gilliland Front Row Ford + 3 laps 32. Andy Lally TRG Chevrolet + 3 laps 33. Dave Blaney Baldwin Chevrolet + 3 laps 34. Mike Bliss FAS Lane Ford + 3 laps Retirements: Clint Bowyer Childress Chevrolet 259 laps Jamie McMurray Earnhardt Ganassi Chevrolet 198 laps Scott Wimmer Gordon Dodge 90 laps Tony Raines Front Row Ford 38 laps Joe Nemechek NEMCO Toyota 37 laps JJ Yeley Whitney Chevrolet 35 laps Michael McDowell HP Toyota 32 laps Scott Riggs Whitney Chevrolet 28 laps Mike Skinner Germain Toyota 17 laps