The European Tour regular, making his first appearance on the OneAsia Tour, fired a five-under-par 67 around Suwan Golf & Country Club for an 18-under total of 198 -- a stroke ahead of Taiwan's Chan Shih-chang (68).
Thailand has not produced a home winner of the National Open since Boonchu Ruangkit won for the second time in 2004, but overnight leader Prom Meesawat (72) and Wisut Artjanawat (71) are well in the hunt, three shots behind the leader, along with Korea's Lee Dong-Hwan (67) and Aussie David McKenzie (70).
Wood, 24, has two top-three finishes on the European Tour this year, but is still seeking his first professional win.
"I played in Malaysia earlier this year and it was so hot and humid that I said 'never again'," Wood, who is 1.96 metres (6 ft 5 inch) tall, was quoted as saying by OneAsia.
"It was getting like that again here today, but I really concentrated on keeping cool -- staying in the shade and using a damp towel all the time."
Wood almost came unstuck at the last after his approach shot from an awkward lie nearly went in the water, but he scrambled par to ensure he was alone atop the leaderboard.
"I will just try to play the same again tomorrow," he said. "I won't worry what anyone else is doing and just concentrate on my own game."
A shot further back, Chan is surprised he is in Thailand at all -- never mind challenging for the title.
The 26-year-old only landed a spot in the field following the late withdrawal by a member of the Japan Tour, who were given 20 slots as part of a growing relationship with OneAsia.
"I have the chance to win my first championship on a tour and that's my aim this season -- whether on the Asian Tour, Japan Challenge Tour or OneAsia," he said.
Defending champion Andre Stolz of Australia, who won the OneAsia Order of Merit title last year, is 12 shots off the lead after shooting a 70.
198 - Chris Wood (ENG) 67-64-67
199 - Chan Shih-chang (TPE) 65-66-68
201 - Lee Dong-Hwan (KOR) 67-67-67, David McKenzie (AUS) 65-66-70, Wisut Artjanawat (THA) 66-64-71, Prom Meesawat (THA) 66-63-72
202 - Boonchu Ruangkit (THA) 69-66-67
203 - Kim Meen-Whee (KOR) 69-68-66, Udorn Duangdecha (THA) 70-65-68, Arnond Vongvanij (THA) 67-67-69, Rohan Blizard (AUS) 67-65-71