He stands two strokes clear of Dave Eichelberger, who also shot a second-round 65 to get to 13-under-par 131. Fuzzy Zoeller and defending champion Dana Quigley posted matching rounds of 7-under 65 to share third place at 12-under-par 132.
Tewell, one of 12 players to complete their first rounds Saturday morning after play was suspended due to darkness on Friday, birdied two of his final four holes to close his first 18 at 8-under 64.
The 54-year-old opened quickly with a birdie on the first at Hualalai Golf Club. He came back three holes later with a two-putt birdie on the fourth that got him to 10 under.
After five straight pars, Tewell birdied the par-5 10th. He moved to minus-12 with a two-foot birdie at the 13th and made it two straight with a two-putt birdie on No. 14.
'I struggled a little bit in the middle of the round,' said Tewell. 'When I was two-under at the turn, I knew I had to play better coming in.'
Tewell, who won the Farmers Charity Classic last year, drained a 15-footer for birdie on the 16th to take a one-shot lead on Eichelberger.
Tewell capped his second bogey-free round with a six-foot birdie putt at the last to take a two-shot lead into the final round. He is in good position as 15 of the last 20 MasterCard winners have held at least a share of the lead heading to the final round.
'I gave it all I had. I had a kidney stone attack about 3:00 AM,' said Tewell. 'I'm feeling fine now. No lead is safe though. Someone can shoot 9- or 10 under.'
Eichelberger, one of six players to shoot 65 on Saturday, also opened with a birdie at the first. He later rolled home a 20-foot birdie putt at the fifth to move to minus-eight. The 2002 Emerald Coast Classic winner two-putted for birdie at the seventh, his third birdie of the day.
The 60-year-old climbed to 10 under with a two-putt birdie at the par-5 10th. He converted an 18-footer for birdie at the 12th and moved to 12 under with a birdie on No. 14.
Eichelberger capped his round with an eight-footer for birdie at the 17th. His birdie try at the last slip by the edge.
'It's a birdie contest with perfect conditions,' said Eichelberger. 'It's going to take 18 under, possible 20 under to win.'
Bruce Fleisher also posted a 7-under 65 Saturday to move to 10-under-par 134. He shares fifth place with Jack Nicklaus (66), Gil Morgan (67) and Tom Purtzer (67).
Craig Stadler, Stewart Ginn and Tom Jenkins are one stroke further back at 9-under-par 135.
James Mason, who held the overnight lead before Tewell overtook him Saturday morning, managed just an even-par round of 72. He stands at 7-under-par 137.