Lewis, the reigning LPGA Player of the Year, was at 11-under 133 at Sentosa Golf Club.
She led a pack of six players tied for second: Ariya Jutanugarn (66), Na Yeon Choi (66), Chella Choi (67), Paula Creamer (67), Sun Young Yoon (68) and overnight leader Azahara Munoz (70).
Top-ranked Yani Tseng stumbled with a double bogey on the par-5 4th hole and shot a 73. She was in tie for 21st at 3 under.
Lewis has started the new season with the same form that saw her win four titles last year and climb to fourth in the world rankings.
The 28-year-old American also held the 36-hole lead last weekend at the LPGA Honda Thailand tournament—matching her career-best round of 63 in the process—before shooting a 76 in the third round and winding up in third place.
She blamed the lapse on bad putting. She's not going to put the same pressure on herself this time around.
"Last week, my putter just went sideways," she said. "I don't know what happened. But I feel a lot more comfortable with my putter this week, which I'm happy about.
"You can't force things, and last week, I definitely was trying to force some putts and hit them too hard and through breaks, so it's really for me just staying patient tomorrow."
Jutanugarn is also trying to put last weekend behind her. The 17-year-old Thai player has shown no lasting effects from her final-round collapse at the tournament in Pattaya, Thailand, where she blew a two-stroke lead on the 18th hole and lost the title to Inbee Park. She was in tears after the defeat.
The former top-ranked amateur made six birdies in a bogey-free round Friday in her 66—matching Lewis and Choi for best round of the day.
"Today my irons helped me a lot," she said. "I still miss some short putts but my irons, I hit so close to the pin today."
Choi, the reigning U.S. Women's Open champion, briefly surged into the lead by making three birdies at the start of the back nine before bogeying the 15th.
The 25-year-old South Korean, currently ranked second, has inched closer to Tseng's No. 1 ranking since last season, but she's trying to keep this out of her mind.
"I don't know (for) what reason, but I feel very happy to play golf right now and I feel like I don't really have the pressure," she said. "Just like beginning of the season, I can just go out there, play, have fun and I talk a lot with the players."
Given her recent form, Lewis is also eyeing the No. 1 spot this year.
"Middle of last year, that was one of my goals was to track down Yani," she said. "I didn't play well last weekend, but I still finished third and that helps me in that move to No. 1."
Tseng, who has held the top ranking for 107 weeks, seemed almost invincible winning four majors and back-to-back LPGA Player of the Year awards in 2010-11.
But the 24-year-old Taiwanese player hasn't captured a trophy in nearly a year and acknowledged on Thursday that she hasn't felt calm or patient on the course at the start of this season. She managed just one birdie Friday in her 73.
Michelle Wie also struggled, making four bogeys on her first five holes and six overall to shoot at 75. She's at 2-over 146.
Defending champion Angela Stanford also struggled for the second straight day, matching her first-round 76 to sit at 8-over 152 overall. She's in a tie for 59th place in the 61-player field.