Japan's Hidemichi Tanaka, who held the lead after the opening round, managed an even-par 70 to join Tom Byrum and Kenichi Kuboya in a tie for second at 4-under-par 136.
Howell was one stroke off the lead to start the day at Hamilton Golf & Country Club and was relatively quiet early on. Playing the back nine first, Howell parred his first seven holes before picking up his first birdie of the day at the par-5 17th.
'This golf course, it reminds me a bit of a major-type feel,' said Howell. 'If you look at the scoreboard, I think you can see that.'
The 24-year-old, who earned his breakthrough victory on the PGA Tour at last year's Michelob Championship at Kingsmill, found trouble around the turn at the par-4 third.
Howell hit a 5-iron off the tee into the rough and left his second shot in a bunker on the right en route to a bogey. Howell responded at the very next hole and reached the green in two at the par-5 fourth.
He two-putted for a birdie and knocked a 9-iron to 20 feet at the par-4 seventh. The Georgia native ran home the putt for his third birdie of the day en route to the 36-hole lead.
'It was a good day today,' said Howell. 'This golf course is not easy. It rewards par and there are a few holes out there where I left birdie chances out there, but still, making par is still just fine.'
Byrum started at No. 10 and tallied back-to-back birdies from the 15th to jump to minus-5. He found trouble with a bogey at the first but responded with back-to-back birdies starting at the third to climb to 6 under.
The 42-year-old was unlucky at the very next hole, however, and walked away with a double bogey at the par-4 fifth.
Fred Funk shot a 68 to finish two shots off the lead at 3-under-par 137 along with Tom Lehman, Briny Baird, Kelly Gibson and Loren Roberts.
Mike Weir, who is seeking his first victory at this event amidst standing ovations from the galleries, played the back nine first and dropped his tee shot inside eight feet for a birdie at the par-3 13th.
At the very next hole, Weir's second shot gripped the edge of the fringe and he chipped in for a birdie to move to 3 under.
He faltered with a bogey at the 17th but recovered at the second after his approach stopped three feet from the cup. He bogeyed the following hole and parred his way in for a round of 69.
Weir was joined by Steve Allan and Paul Azinger at 2-under-par 138. Azinger would have finished in the group at minus-4 were it not for a penalty at the closing hole.
After Funk chipped from off the putting surface, Azinger's caddie lifted the pin while the ball was still rolling. That penalty cost Azinger two strokes.
Adam Scott, who earned his first victory on the PGA Tour last week at the Deutsche Bank Championship, managed to survive the 36-hole cut on the number along with Vijay Singh, who rallied with a second-round 67 to make the weekend at 3-over-par 143.
Among those who failed to qualify were Ian Leggatt, Mark O'Meara and last year's champion John Rollins.