Italian Manassero, Scotland's Marc Warren and former champion Simon Khan went into extra holes after finishing tied on 10 under par at Wentworth, 2010 winner Khan setting the clubhouse target after a closing 66 that no-one could overtake.
Warren was eliminated on the first play-off hole after his drive finished in an unplayable lie in the trees and his fourth shot found the water guarding the green, with Manassero and Khan both making birdies on the par-five 18th.
Two more visits to the 18th failed to identify a winner, but when Khan's approach plunged into the water on the fourth extra hole, Manassero's two-putt birdie was enough to claim the £666,000 first prize and a fourth European Tour title at the age of 20.
McIlroy, who was 19 when he won his first title in Dubai, wrote on Twitter: "Massive congrats to @ManasseroMatteo!! Makes me feel like an old man! #phenom."
"I'm happy that he wrote that tweet," Manassero said. "I've got so much respect for Rory. I think he's got the best game, the most talented player out here."
Manassero, who at 20 years and 37 days beat the previous record of Bernard Gallacher, who was 20 years and 97 days when he won in 1969, added: "I feel unbelievable, really emotional. It's been an amazing week. I have always felt something really special about this place and this tournament.
"Everything has come together this week. I managed to play well and managed to stay in contention after a tough day on Friday and pulled it off with this play-off. I am the happiest man in the world right now."
Manassero began the day two shots off the lead but carded four birdies and one bogey to be out in 32, rounding off the front nine in style by holing a bunker shot on the ninth.
A bogey on the 11th was followed by a birdie on the 13th, but his best chance of victory seemed to have gone when he was unable to birdie either of the closing par fives to finish alongside Khan and playing partner Warren.
"I was less tense in the play-off than walking the last few holes because you have done all you can in 72 holes and the rest is about trying to hit good normal shots," added Manassero, the first teenager to win three European Tour events when he claimed the Singapore Open in a play-off last year.
"I hit four good tee shots in the play-off and on the 18th that is the most important thing."
Warren was left to rue another missed opportunity after a bogey on the 15th ultimately proved costly. The 32-year-old bogeyed four of the last five holes in the recent Spanish Open to finish one shot outside the play-off and also squandered a three-shot lead with four to play in last year's Scottish Open.
"The other two occasions I felt as if I probably gave those away. This time, I didn't do that," Warren insisted. "I've done absolutely nothing wrong this week, and it's all positives and looking forward to my next event."