Homa chipped in on the final hole before Willett three-putted from close range to finish a shot behind his playing partner.
Willett birdied the first and fourth and when he hung his approach at the eighth up over the flag and watched it trundle back within three feet, a third gain was assured.
He gave that shot back immediately to take some of the shine off a strong outward nine but a 16-foot putt at the 10th curled in and he holed from a similar distance from the fringe of the 14th green for another birdie.
Homa bounced back from two bogeys in the first four holes with three consecutive birdies around the turn, crowned by a 30-foot putt at the 11th.
He came up short with a bunker shot at the last but rattled his chip in off the flag to finish 16-under par and put pressure on Willett's short birdie putt - and amazingly the Englishman twice lipped out from inside five feet for a three-putt bogey that condemned him to a runner-up finish.
Willett could only laugh at his nightmare finish as he shook hands with Homa, who told Sky Sports: "The last three minutes are kind of a blur.
"I played solid - Danny and Justin (Lower) both played well but that was a wild finish."
Homa is part of the American team for next week's President's Cup and said: "I've had a few guys tell me that if the LIV guys hadn't left I wouldn't have made the President's Cup team, so I had a little bit of a chip on my shoulder this week."
Taylor Montgomery produced the round of the day, eight birdies and no bogeys in a 64 to finish third on 13 under.
Overnight leader Lower, playing in the final group with Willett and Homa, shot 73 to finish alongside South Korea's Byeong Hun An a shot behind Montgomery.