Geoff Ogilvy, who won the WGC-Accenture Match Play title two weeks ago, also closed with a 69 to take second place at 10-under-par 278.
Donald was in a tight battle all day. He drained a birdie on the first to get to minus-10, which gave him a one-shot lead. He ran in a 20-footer for birdie on the fourth.
That birdie gave him a brief two-shot cushion, but Mayfair matched Donald's birdie to get back within one. Mayfair dropped a stroke on the sixth.
Donald three-putted for bogey on the seventh to slip to minus-10, one ahead of Mayfair, Jeff Gove and Ogilvy.
Gove made a run at the lead with birdies on the sixth and ninth to move to 10 under. Donald tripped one behind Gove when he bogeyed the 10th. Gove began his fall off the pace with a bogey on 13. After that, he played the final five holes at 3 over to fall to seventh place.
'I was struggling on the greens (early on the back nine) and had lost a little bit of confidence and had a couple three-putts in a row, but I was still right there,' said Donald, who collected $990,000 for the win. 'I knew if I played my golf that hopefully it would be good enough.'
Donald climbed back into a tie for the lead at minus-10 with a 10-foot birdie putt at the 13th. His co-leader was Ogilvy, who birdied 13 and 14 to grab his share of the lead.
The big swing came as Ogilvy played 15 and Donald No. 14. Ogilvy, playing two groups ahead of Donald, missed the 15th green and hit a poor pitch and that led to a bogey to dropped him to 9 under.
Donald drained a 26-footer for birdie on 14 to take a two-shot advantage. Ogilvy fought right back with a 10-foot birdie putt on the 16th. Just after Ogilvy could not convert a birdie try on the par-five 17th, Donald missed a 17-footer for birdie on 16.
The Englishman two-putted for par on the 17th and Ogilvy did the same on 17 and 18.
Donald closed out his the win with a fabulous approach to the 18th. His second shot stopped 4 feet from the cup and he sank the birdie putt to close the event in style and pick up his second PGA TOUR win.
'It's nice to finish with a great shot like that,' Donald said. 'It was a nice way to finish up. It looked pretty good in the air. I had a little mud on the ball, so I was hoping it would fly straight. I had a perfect yardage and it came off beautifully.'
Dudley Hart, like the winner, closed with a 69 to grab sixth place at 7-under-par 281. Gove's late struggles gave him a 2-over 74. He finished alongside Frank Lickliter and Stephen Ames at minus-6.
D.A. Points and Mathew Goggin shared 10th place at 5-under-par 283. Padraig Harrington, the 2005 champion, closed with a 74 to share 16th place at minus-2.