McIlroy will be bidding to complete a career grand slam at Augusta National and the Northern Irishman ensured he will be among the leading contenders after a majestic final round of 64 at Bay Hill.
The 28-year-old was particularly imperious over the back nine, in which he nervelessly recorded five birdies in his final six holes to finish on 18 under par for a three-shot victory over Bryson DeChambeau.
He arguably saved his best for last, holing a putt from more than 25 feet on the 18th before raising his arms aloft.
The last time McIlroy reigned supreme was at the Tour Championship on September 25, 2016 - the same day Arnold Palmer died - and he returned to winning ways at the resort once owned by the golfing great.
Tiger Woods was briefly in contention for the second successive Sunday after three birdies in the space of four holes immediately after the turn, but his challenge faded with bogeys at the 16th and 17th, and he finished in a share of fifth.
McIlroy told Sky Sports golf: “I played a perfect round of golf.
“It was awesome to feel the buzz of being somewhere around the lead going into the back nine and reeling off those four birdies in a row.
“I’ve missed it, I really have missed it, and to play the sort of golf that I played today under that pressure, I’m really proud of myself and just so happy to win.
“It’s ironic to think that the last time I won was when Arnie passed away. To be able to create my own little piece of history on the 18th green here was pretty special.
“I’m just so happy to be back in the winner’s circle again and win a tournament that has Arnold Palmer’s name on it, someone that means so much to us in the game of golf.”