Defending champion Bob Gilder and 2000 winner Gil Morgan share second place after rounds of 4-under-par 66.
Bobby Lincoln, Doug Tewell, Jim Ahern and Walter Hall are tied for fourth at minus-3.
Zoeller, who won the season-opening MasterCard Championship, wasted little time in breaking into red figures. He knocked a 9-iron to 6 feet to set up birdie at the first.
He used a string of great iron play near the end of his front nine to move up the leaderboard. Zoeller, who won both the Masters and U.S. Open on the PGA Tour, hit a 9-iron to 3 feet for birdie at six, then blasted out of a bunker to 3 feet to set up birdie at the par-5 seventh.
At the par-3 eighth, Zoeller played a 7-iron to tap-in range to reach 4 under par for the championship.
'I hit the ball close on the front nine,' said Zoeller. 'There were a lot of cross winds on the back nine.'
Those winds certainly affected Zoeller. He made only one birdie, a 3-footer at the 13th, but it was still enough for the 52-year-old to take the first-round lead.
Zoeller missed the cut last week at the Masters and felt his swing was in disarray. He noticed a change in Thursday's practice round and it showed on the scorecard Friday.
'I could feel the swing coming back yesterday,' said Zoeller. 'I drove the ball good. I didn't do that last week. It's nice to play out of the short grass for a change.'
Gilder, who won this title by four shots last year, collected two birdies on the front side and went 3 under with a tap-in birdie at the par-5 11th. He knocked a pitching-wedge to 2 feet for his fourth birdie at 13 but three-putted from 80 feet for a bogey at the next hole.
Gilder drained a 6-footer for birdie at the 17th to join Morgan in a share of second place.
'I've made my share of mistakes but today I didn't do it,' said Gilder, a seven-time winner on the Champions Tour. 'There's a little more pressure on the defending champion. I'm glad I got off to a good start today.'
Morgan did all of his damage on the front nine. He tallied three birdies in his first four holes, then rolled home a 15-foot birdie putt at the par-3 eighth.
He recorded 10 straight pars, including a great save at 16, to stay near the lead.
'I started off pretty good,' stated Morgan, who won the SBC Classic in mid- March. 'I don't know why I play good here. I guess it's a horses for courses thing.'
Fifteen golfers are tied for eighth place, including Gary Koch, Wayne Levi, Tom Jenkins, Dave Eichelberger, Tom Purtzer, J.C. Snead, Rodger Davis and Jerry Pate.
Hubert Green returned to the Champions Tour on Friday. He last played at the MasterCard Championship in mid-January and has since undergone treatments to aid his recovery from a cancerous growth on his throat and tongue. Green shot a 10-over-par 80.