Hamlin had to work hard for the win at Michigan International Speedway after being relegated from pole position to the rear of the field for unapproved changes between qualifying and the 200-lap race.
The Joe Gibbs Racing driver at one point during the race found himself spinning on Lap 83 when a nose-to-tail accordion effect triggered a multi-car accident.
Hamlin escaped without damage and rallied to finish Stage 2 in eighth.
He remained a factor for the final stage, and with 38 laps to go made the decisive move for the lead when he went three-wide with Spire Motorsports duo Daniel Suarez and Carson Hocevar.
Hamlin was untouchable in the final laps as he built an 11-second lead over Legacy Motor Club driver Erik Jones, who was a late charger to the runner-up spot.
Michigan marked the 63rd win for Hamlin, levelling him with the late Busch.
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“This Joe Gibbs Racing team just keeps giving me amazing race cars,” said Hamlin.
“This Toyota was just amazing. At the last run there it just hammered down.
“I had a few good restarts and then once we got to the lead I was going to lay it out, all I had.”
With 63 Cup Series wins, Denny Hamlin ties Kyle Busch at 9th on the all-time wins list.
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Hamlin was given a commemorative flag after the win, which bore #18 on it – combining Busch’s stylised #8 that he ran at Richard Childress Racing and the #18 that he wore with Joe Gibbs Racing.
Hamlin noted how hard the last year had been for him and the wider NASCAR fraternity.
He lost his father in a house fire during the off-season that also left his mother badly burned.
NASCAR also lost icon Greg Biffle at 55 years old in a plane crash that claimed seven lives, including his wife and two children.
Busch’s recent death at 41 years old to illness rocked the community to its core as the first active driver to die since Dale Earnhardt in 2001.
This week, NASCAR Hall of Fame driver Ned Jarrett died at 93 years old.
“The off-season was rough for me, it was rough for the NASCAR family, we lost a lot of people,” said Hamlin.
“This week we lost gentleman Ned [Jarrett], the original bad-ass of the #11.
“We’re still thinking of Kyle, Samantha, Brexton, Lennix.
“Just an unbelievable feeling to be able to strap in every week and I don’t take it for granted this opportunity that I’m in.
“I just love that we’re making the best of it.”
NASCAR continues its season at the “Tricky Triangle” Pocono Raceway on June 15 AEST.
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