The 34-year-old American, three times a runner-up on the PGA Tour this season, had eight birdies in 11 holes before a closing bogey left him 14 under par and two ahead of South African Jbe Kruger.
Also round in 64, world number 181 Kruger out-scored playing partner Tiger Woods by three to keep alive his hopes of the massive £806,000 first prize.
Woods improved from joint seventh to tied fifth, but is now five strokes behind rather than three.
As for first-round pacesetter Troy Matteson, he did not have a bogey for the second day running, but his only birdies came at the third and sixth holes and with a 69 he dropped into a tie for third with Australian left-hander Greg Chalmers.
Garrigus had to wait until the short seventh for his first birdie, but then rattled off four in a row and continued to make forward progress over the back nine until his slip-up at the last.
Woods added six birdies to the seven he had on the opening day, but once again there were also two bogeys on his card.
Scotland's Martin Laird birdied three of the final five holes for a 67 and joint 11th place on seven under, while Swede Carl Pettersson is one further back after a round that included an eagle, six birdies and four bogeys.
Disappointment for the home fans came with Danny Chia managing only a 75 and crashing from seventh to 41st in the 48-man field.
Woods, chasing a fourth victory of the year, again endured a frustrating day on the tricky greens at the Mines Resort. But he was impressed with what he saw from Kruger.
"I knew a little bit about him, but I hadn't seen him play. Today was the first time I've seen him. He was playing right in front of us yesterday, and he had a seven under with one to go and made a big mistake at 18. But he's playing well. What is he? 12-under-par with a double. So he's playing really, really well," said Woods.
The American superstar, making a return to Malaysia after winning the 1999 World Cup of Golf, battled hard in the heat and humidity to keep alive his hopes of winning in his CIMB Classic debut.
"That's one of the hard things," said Woods. "You have to make birdies out there. You can't just be passive and play to the centre of the greens and stuff. You have to be aggressive. Guys are taking it low.
"It was just one of those days that I didn't make enough birdies. I didn't really have a lot of looks, and then the looks I did have were downhill, cross grain putts and putts that I just couldn't be aggressive with."
Garrigus, a one-time winner on the PGA Tour, reckons the winning score will be 20-something under par after shooting his second straight 64.
"I feel like I can beat anybody in the world. I've played with Tiger. I've played with Rory (McIlroy) in the TOUR Championship. I hit it just as good as those guys. It's just the short game. If I'm putting well and if I keep putting like this on the weekend, it's going to be hard to catch me," said the 34-year-old
"I do have a very high confidence level right now. I had one of the best years of my career. I'm having fun, having a good time with it. A lot of my hard work is paid off and that's nice to see."