Rose birdied the opening par-5 hole, reeled off four birdies in a row starting at the par-3 fourth, followed with 10 pars in a row and finished by sinking a curling downhill 5-foot birdie putt at 18 for his second 65 in a row.
"I was aware I hadn't made a birdie for quite some time so it was nice to finish off the round like that," Rose said.
The bogey-free round put the 30-year-old Englishman on 13-under par 200 through 54 holes at the $5.5 million tournament, one stroke ahead of Zimbabwe's Brendon de Jonge and American Webb Simpson.
Rose won his first US titles last year at the Memorial and National, the top US tuneup events for the US and British Opens, and could strike again three weeks ahead of the Masters.
"I decided to play this week and next heading into the Masters to try and drop some shots on the way to Augusta," Rose said. "No doubt this week has been one of the best (for striking the ball)."
Rose went five-under for his last nine holes Friday and his front nine Saturday, what would have been a 10-under 61 had they been paired.
"I'll take that as an unofficial round," Rose said. "The first 27 holes I had to be patient. Nothing was happening for me. After that, it seemed like everything started happening all at once. It's going really well for me."
De Jonge opened and closed the front and back nines with birdies and added another at the par-5 11th to complete a run of three in a row in a bogey-free round of 66 in quest of his first US PGA title.
Simpson birdied three of the first five holes, followed with another at 11 and answered bogeys at 13 and 15 with birdies at 16 and 17 and missed a 30-foot birdie bid at 18 by inches to settle for his third consecutive round of 67.
Scott Stallings, who missed the cut in five of six prior starts in his first PGA campaign, aced the par-3 eighth hole on his way to a five-under par 66 to share fourth with fellow American Gary Woodland on 202.
Stallings, trying making the most of his sponsor's exemption entry this week, made his first PGA cut last week at Puerto Rico.
"It's about time I played some good golf," Stallings said. "Some good people have been helping me out and it's time I brought some of that to the course."
Stallings, who turns 26 on Friday, took a bogey at the second hole but answered with a birdie at the par-5 fifth before his hole-in-one, which came after birdies on the hole the first two days.
"I thought it was close and then when we got up there we saw it was in the cup," Stallings said. "It's pretty cool. That's my first one in a tournament."
Stallings sandwiched birdies at 10 and 11 around a pair of bogeys but birdied the par-3 13th and 15th holes and added another at 16 to keep pressure upon Rose.
Woodland birdied five of the last eight holes to fire a 67.
"I've been hitting the ball well all week," Woodland said. "On the back nine, finally I got some putts to go in."
Nick Watney, who won last week's World Golf Championships event at Doral, fired a 65 to share sixth with fellow Americans Brandt Snedeker, Garrett Willis and Chris Couch.