McIlroy, 30, carded a final-round 66 to finish on 18 under par, four shots clear of second-placed Xander Schauffele and five ahead of third-round leader and world number one Brooks Koepka at East Lake Golf Club.
He pockets $15m (£12.2m) – a prize fund he has previously questioned.
“To play like that alongside Brooks and win, it’s awesome,” said McIlroy.
Speaking to the Golf Channel, he added: “My goal today was to win by even strokes. My goal was to shoot the lowest score of the week and I think with the birdie on the last I did that. That’s why I was concentrating so much. It’s such a cool way to end what has been a great season.
“I’m very proud of this and I’m going to enjoy this one.”
American Koepka had held a one-shot lead after a weather-delayed third round in Atlanta, during which six people were injured after two lightning strikes.
But he hit a double bogey on the seventh hole and carded three further bogeys on the back nine to finish in a tie for third with compatriot Justin Thomas.
England’s Paul Casey finished fifth on nine under par.
McIlroy defies radical new format
McIlroy began the week on five under par – five shots behind Thomas, who led the FedEx Cup standings going in to the season-ending Tour Championship.
In a change to the rules for 2019, players entering the final event were awarded a starting score based on their FedEx Cup rank, which descended from -10 for the leader, down to level par for players ranked 26-30.
McIlroy, who won the FedEx Cup and Tour Championship titles in 2016, was tied for second with American Schauffele on 14 under going into the final round and started, as did Koepka, with five straight pars.
He made a birdie on the par-five sixth before taking advantage of Koepka’s double bogey on the seventh, holing another birdie from 20 feet.
Two further birdies followed on the 12th and 13th to go four strokes clear and despite two bogeys, he all but sealed his 17th PGA Tour win on the penultimate hole, carding another birdie before picking up another shot on the 18th.