Having slipped down to 90th in the world rankings, Harrington put recent woes behind him with a blistering round.
The three-time major winner started with back-to-back birdies at Innisbrook, finished with three in a row and had five more in between to take one shot off the course record.
“It’s been a strange last year, but I’m very comfortable where my game is at,” Harrington, who is looking for his first victory on the PGA TOUR since he won The Open Championship and PGA Championship in 2008, told PGATour.com.
“For a long time now, I play better on the Monday, Tuesday, Wednesday than I do on the Thursday, Friday, Saturday, Sunday. I’m trying to stay patient. I know my game is good. One of the hardest things is to wait with confidence.”
Harrington’s three closing birdies included a 74-foot, 11-inch birdie on the 17th, the longest putt of his PGA Tour career by almost 10 feet.
“I would like to tell you it was funnelling right up the green and couldn’t go anywhere else,” Harrington said about the putt. “But certainly the last 15 feet it was right in the middle of the hole. That’s a bonus obviously.”
Harrington, who had a hole-in-one during the eve-of-tournament pro-am, led by three from American Will Claxton, who eagled the 14th and birdied the 18th to sign for a 64, while nobody else managed better than a 66.
A bogey on the 18th saw Kenny Perry drop back into a seven-way tie for third alongside Cameron Tringale, John Senden, Jason Dufner, Jason Bohn, Jim Furyk and William McGirt, all on 66.
World number two Luke Donald, along with compatriot Justin Rose, was part of a large group one shot further back on 67.
Masters champion Charl Schwartzel had a miserable day, 15 strokes back from the lead, while Sergio Garcia shot 68, Brian Davis 69, Paul Casey and Greg Owen 70 and Martin Laird 73.