Tom Watson, Tom Kite, Bruce Fleisher, Morris Hatalsky, Wayne Levi and David Eger finished in a tie for fifth at 4-under-par 68.
Zoeller stumbled out of the gate with a bogey at the second at The Reserve Vineyards & Golf Club but recovered with two straight birdies starting at the fourth.
'Some people push the red button when they bogey one of the first couple of holes,' said Zoeller, who tied for 19th at this event last year. 'But I was just getting started.'
The 51-year-old surged to the top of the leaderboard on the inward half. Zoeller picked up three consecutive birdies from the 10th and added a birdie at the 15th to move to 5 under.
Zoeller, whose only Champions Tour victory came at the Senior PGA Championship in 2002, knocked his third shot within inches of the cup at the 16th and tapped in for birdie and the lead.
'I played very, very well,' said Zoeller. 'I hit some very close shots, I was able to make the small putts, which you have to do out here.'
Ahern's birdies came in streaks on Thursday. He ran off three straight starting at the fourth before dropping a shot at the seventh.
He added a birdie at the 12th and got another streak going with back-to-back birdies from the 16th. At the par-5 last, Ahern converted a six-foot putt for a birdie and his share of first.
Irwin, who has missed significant time this season due to back problems, picked up two birdies on the front nine before catching fire down the stretch.
The 58-year-old birdied the 15th and landed his second shot just off the putting surface at the par-5 16th. The all-time winner on the Champions Tour chipped to three feet and ran home the short putt for a birdie to move to minus-four.
At the par-4 17th, Irwin dropped his approach inside two feet and tapped in for his third consecutive birdie.
'I hit enough nice putts to salvage a very good round,' said Irwin. 'On paper it looks very good.'
Watson, who has played well in the majors this year including a win at the Senior British Open, tallied two birdies on his front nine and added a pair of birdies on the inward half to finish two shots off the lead.
Defending champion Jim Thorpe put the pressure on Zoeller with two birdies, an eagle and a bogey over his first nine holes.
Thorpe took the outright lead after three birdies on the back side lifted him to 6 under but the six-time Champions Tour winner found trouble on his closing holes.
Thorpe bogeyed the 16th and double-bogeyed the par-4 17th to finish with a round of 69.
He was joined by Des Smyth, Gil Morgan, Mike Smith, Bob Eastwood, Kermit Zarley, Bobby Wadkins, Mike McCullough, Larry Nelson and Dave Barr at 3-under par.
Bruce Lietzke, who won the U.S. Senior Open this year, was part of a group at 1-under-par 71 that included Craig Stadler, this year's Ford Senior Players Championship winner.
Jack Nicklaus, who is a four-time winner of this event, managed three birdies and three bogeys for an even-par round of 72.
John Jacobs, the 2003 Senior PGA champion, struggled with an opening-round 77.