The 47-year-old, who has led on all three days at the Alpine Golf Resort-Chiangmai, mixed six birdies and an eagle with two bogeys for a 54-hole total of 18-under-par 198.
Prayad's countryman Thongchai Jaidee and Australia's Matthew Stieger, who continued his bogey-free streak, were at 13-under 203 in the $750,000 event in Thailand.
Yang Yong-eun, the first Asian man to win a major, was among six players a shot further behind, while four-times major winner Ernie Els of South Africa carded a six-under-par 66 to move up to tied 15th place.
The smooth-swinging Prayad, whose round was highlighted by a chip-in eagle on the seventh hole, briefly lost his touch with two consecutive bogeys on the 15th and 16th hole but regained his composure with a birdie on the 17th.
"I have a five-shot lead now and I will play steadily and not be aggressive," Prayad, chasing his seventh title on the Asian Tour, said.
"I think the pressure is on those chasing me. They need to have a good front nine or else they won't be able to catch up with me.
"I made mistakes but it doesn't matter. I was careless on 16 but I still think I have a very strong advantage."
Thongchai, ranked 59 in the world, hit five birdies against two bogeys in the third round and needs a win on Sunday to have a chance of qualifying for the Masters in two weeks' time.
"I think the problem was my putting and reading the lines," the three-time Asian number one, said.
"I hit a lot of good shots but the greens are killing (me). They are tough to read. Prayad played so well. He dropped a couple of shots but he came back.
"He likes the course and he's in form. He's got a good chance. I'll try my best but I'll need luck tomorrow."