Hoffman, the joint midway leader alongside fellow Americans Steve Le Brun and Kevin Streelman, enjoyed a blistering start with four birdies over his first five holes at Harbour Town Golf Links.
A steady stream of pars followed over his bogey-free round, which was helped along by a further birdie on 15, as the 36-year-old advanced to 11 under par overall - two strokes clear of nearest challenger Webb Simpson.
US Open champion Simpson carded a six-under-par 65, collecting three birdies on the outward nine and three on the back nine to put himself firmly in contention for Sunday.
Streelman was three shots off the pace after a 69, with Northern Ireland's Graeme McDowell (68) and Zimbabwe's Brendon de Jonge (67).
McDowell responded well after bogeying the par-four third, getting back on track with birdies at five and six and rounding things off by picking up a final shot at the 18th.
Hoffman told www.pgatour.com afterwards: "I would say I wasn't mature enough to play this golf course.
"I didn't understand how to play it. I guess I would get frustrated when I hit the fairway and didn't have a shot at the green."
"It was definitely the best playing round I've had in a long time."
Streelman said: "I don't have much to lose. I'm going to see what the course can give us."