Dana Quigley, the 2003 champion who played the final two rounds with Zoeller, posted a 65 to finish alone in second place at 19-under-par 197.
Craig Stadler tied the course record of 63 to share third place with Doug Tewell at 18-under-par 198. Tewell, the overnight leader, fought a balky driver throughout the back nine as he closed with a 3-under 69. Tom Purtzer finished two shots further back at 16-under-par 200.
Zoeller began the day three shots off Tewell's lead at Hualalai Golf Club. He dropped further back with a bogey at the second, but he would roar back into contention quickly.
'A great week of golf. I gelled the whole week,' said Zoeller, who earned $268,000 for the win. 'I had a good feeling for this course last year. This course reminds me of Waialae years ago.'
The 2002 Senior PGA champion drained back-to-back birdies from the third to move to 13 under. He continued his move with a long birdie putt at the fifth.
After draining another birdie at No. 6, Zoeller capped a run of five straight birdies with a 15-footer at the seventh that gave him a share of the lead at 16 under.
Tewell moved back into first place with a birdie at the seventh, but he dropped a shot on No. 9 and the lead was Zoeller's as he two-putted for birdie at the 10th. Zoeller again fell behind Tewell as heoeller ran off five consecutive pars.
The turning point came at the par-4 16th. Zoeller converted a 12-footer for birdie to move into a four-way tie for the lead. He made it two straight when he matched Quigley's birdie on 17 as the duo moved ahead of the pack at minus-19.
At the last, Zoeller's tee ball found the fairway, while Quigley found the left rough and an awkward lie. Quigley dropped his second shot in a greenside bunker ,while Zoeller knocked a sand wedge within 18 feet of the cup.
Quigley nearly holed his bunker shot, but had to settle for a tap-in par. Zoeller calmly stepped up to his putt and drained it for his second Champions Tour victory.
'I felt good on that last putt,' Zoeller said. 'I couldn't have left that putt in a better spot on that green. The last three putts I made were unbelievable. I knew I had to birdie that last hole.'
Quigley also began the day three shots behind Tewell. He had a steady front nine with birdies on the two par-5s, Nos. 4 and 7. He climbed to 16 under with birdies at the 10th and 13th.
The eight-time winner on the Champions Tour ran off three straight birdies from the 15th to keep pace with Zoeller, but was unable to hole his bunker shot at the last that would have forced extra holes.
'It was so much fun out there today,' Quigley said. 'It was great golf. Fuzzy just made one more putt than I did. I played well enough to win.'
Stadler posted three birdies and an eagle on the front nine to climb to 14 under. He notched four more birdies on the back nine, including one at the last that gave him a share of the lead before he was passed by Zoeller and Quigley.
Tewell birdied the third and seventh to get to 17 under. His troubles began soon though. He bogeyed the ninth, for his first dropped shot of the event.
He recovered with back-to-back birdies from the 10th, but then missed four straight fairways, one of which led to a bogey at the 13th. Tewell, who had won the four previous events he led entering the final round, erased that mistake with a bogey at the next, but he could not mount a late rally.
While there was a great battle for the lead, a legend was lurking just behind them. Jack Nicklaus bogeyed the third and fifth, but eagled the fourth to stay at 10 under.
Nicklaus, who celebrated his 64th birthday earlier in the week, notched consecutive birdies from the sixth. The Golden Bear climbed to 13 under with a birdie at the 12th and kept climbing with back-to-back birdies from the 14th. However, he ran out of holes and finished alone in sixth at 15-under-par 201, after a closing 67.