Prom was on a two-round 15-under-par total of 129 at the $1 million tournament held at the Suwan Golf and Country Club course, on the western outskirts of Bangkok.
It was a shot better than countryman Wisut Artjanawat and two ahead of England's Chris Wood, Aussie David McKenzie and Chan Shih-chang of Taiwan.
The 28-year-old's father Suthep won the open in 1991, becoming the first Thai to do so.
Since then only one other Thai has won The Thailand Open, the fifth stop on the OneAsia schedule, despite the Kingdom producing some of the region's best players since the tournament started in 1965.
"I am very happy. Everything has been great for the first two rounds," said Prom, nicknamed "Big Dolphin", according to a statement from organisers.
Wisut was also delighted with a perfect round on a course he says suits his game.
"All 18 greens in regulation? That's (the) best round I have had this year for sure," he said. "If I could make one or two putts it would be even better."
Wisut said he was looking forward to playing against Prom on Saturday, noting they had been friends since childhood.
"But on the golf course things are different," he added.
Overnight leaders Yasunori Yoshida and Kim Hyung-Tae followed their opening 64s with second rounds of 72 and 73 respectively, while defending champion Andre Stolz just made the cut after finishing two rounds at four under par.
After round two of the Thailand Open being played at the par 72 Suwan Golf and Country Club:
129 - Prom Meesawat (THA) 66-63
130 - Wisut Artjanawat (THA) 66-64
131 - Chris Wood (ENG) 67-64, David McKenzie (AUS) 65-66, Chan Shih-chang (TPE) 65-66
132 - Rohan Blizard (AUS) 67-65, Choi Jin-Ho (KOR) 66-66, Thaworn Wiratchant (THA) 68-64
134 - Lee Dong-Hwan (KOR) 67-67, Choi Joon-Woo (KOR) 70-64, Arnond Vongvanij (THA) 67-67