Eager to bolster a 10-6 overnight lead, the pair helped settle any nerves from Europe, who encountered a United States side full of determination.
By the time McIlroy and McDowell had beaten Rickie Fowler and Jordan Spieth, the US were up in four matches.
However, early European points helped curtail a US fightback, with world number one McIlroy again proving Fowler's nemesis.
Fowler ran McIlroy close at the The Open in July but found himself 5 down through six holes after the Northern Irishman strung together four birdies and an eagle.
Having made it two wins from three in Ryder Cup singles, McIlroy watched on as his compatriot and former Ryder Cup partner McDowell wrapped up a stunning comeback.
Some questionable McDowell putting saw Spieth move 3 up through five but the Northern Irishman found three back-nine birdies to give Europe a further boost.
McIlroy revealed the final day of the Ryder Cup had, in many ways, proven a bigger occasion for him than the finales of The Open and US PGA Championship.
"I was probably more up for this day than I was the first two. I was just so up for it, there was no option other than to win," he explained.
"I played my best golf of the week. I mean, I started so well, 6-under through six holes. That built a comfortable lead that I was able to hang on to."