The New Zealander birdied two of her final three holes to finish on 17 under par at Tiburon Golf Club in Naples and hold off the challenge of Ireland's Leona Maguire.
Maguire, who held a share of the lead overnight, had to settle for second place after a level-par round of 72, with Sweden's Anna Nordqvist a stroke further back after carding a 67.
Ko's victory saw her claim her second LPGA player of the year title as well the winner's cheque of 2million US dollars (£1.6million).
"I felt calmer than I thought I would be," said Ko at the presentation ceremony, broadcast by Sky Sports.
"There was a lot of things on the line today. I really wanted to play the best golf I can.
"There were so many big names chasing Leona and I. I knew it would be a tough battle, especially with how tough the conditions were as well, but I just focused on my game.
"I just wanted to make my share of birdies."
Ko bogeyed at the opening par five but recovered by holing from 30 feet for a birdie at the third and picked up another shot at the eighth.
She dropped a shot at the 14th after finding the rough by the green but birdies at 16 and 17 saw her secure the title in commanding fashion.
England's Georgia Hall finished in a tie for fourth on 12 under alongside Jeongeun Lee6.