Bruce Fleisher, who won this event in 2000, finished alongside Hale Irwin, Tom Kite and Mark McCumber at 3-under-par 68.
A steady breeze and difficult pin placements offered several challenges during the first round at the TPC of Tampa Bay. McCullough, who tied for seventh at this event last year, started with a birdie at the first.
McCullough dropped a wedge inside 12 feet for birdie at the fifth but found trouble with a three-putt bogey at the par-5 seventh to make the turn at minus-1.
The 57-year-old surged into the lead on the back nine. McCullough two-putted for birdie at the par-5 12th and hit his second shot to six feet for birdie at the 13th. At the par-5 14th, McCullough knocked a wedge to five feet for his third birdie in a row.
McCullough bogeyed the 17th to fall back into a tie for first at 3-under but responded at the following hole. He left his approach 40 feet from the cup and drained the putt to secure the first-round lead.
'The golf course played pretty quick and the greens were receptive,' said McCullough, a two-time winner on the Champions Tour. 'Skill level might be higher and that's why everyone is bunched together. We're all playing from about the same position.'
Irwin, who tied for seventh last week in Naples, played the back side first and had two birdies and one bogey on his first nine holes. He hit a pitching-wedge inside four feet for birdie at the fourth and drained a 12-footer at the sixth to finish just one off the lead.
'I played very well today,' said Irwin. 'I'm pleased with the position I'm starting tomorrow. Today was a tough scoring day.'
Andy North, Mike Hill, Graham Marsh, David Graham and Rocky Thompson were two shots off the lead at 2-under-par 69.
Lee Trevino had two birdies and a bogey to finish one shot further back at 1-under-par-70. Trevino was joined by Bill Rogers, Jim Holtgrieve, Bruce Summerhays, Jay Sigel, Allen Doyle, Dana Quigley, Larry Nelson, Tom Wargo, James Mason, John Jacobs, Mark Pfeil and defending champion Doug Tewell in a tie for 11th.
Jack Nicklaus, who won this event in 1996, had two birdies over his first five holes. He struggled on the inward half, however, with three bogeys and one birdie to finish in a group at even-par 71.
Arnold Palmer was intent on playing this week but withdrew prior to the start of the first round due to back spasms. Palmer, who also pulled out of Thursday's pro-am, had not withdrawn from an event since the 1997 Bay Hill Invitational.