Luke Donald also carded a 65 and stands at minus-13. Louis Oosthuizen matched the 65s that Donald and Howell posted to move to 12-under-par 132.
First-round leader Graeme McDowell stumbled to a bogey on his last hole to close a round of even-par 72. He shares fourth place with Richard Sterne (68) and Jamie Donaldson (65) at 10-under-par 134.
Ernie Els, the second-ranked player in the world, posted his second straight 68 and stands in a tie for 11th at 8-under-par 136. World No. 1 Vijay Singh managed a 2-under 70 to move to 6-under-par 138 and is tied for 29th.
The tournament is using three courses as it has a pro-am competition for the first three rounds. Play is contested at the Old Course at St. Andrews, Carnoustie Golf Club and Kingsbarns Golf Links. Players will rotate over the three courses for the first three rounds, before the final round is contested at St. Andrews.
Howell played St. Andrews on Friday and started on the 10th tee. He birdied his first, but tripped to a bogey at the very next hole. Howell came right back with a birdie at the 12th.
The Englishman made it two in a row as he rolled home a birdie on the 13th. Howell capped a run of three straight birdies on No. 14 to get to minus-10.
Howell closed his opening nine in style as he flew a sandwedge right into the hole at the 18th for eagle. His momentum was short-lived as he tripped to a bogey at No. 1.
The 29-year-old Howell, who played on his first Ryder Cup team last month, bounced back with consecutive birdies from the second to get to 13 under. He cruised to five straight pars before birdieing the par-4 ninth from 5 feet out to grab the overnight lead.
'Because of the Ryder Cup there are a number of feel-good factors and I think most guys feel good about themselves at the moment,' said Howell, who won the 1999 Dubai Desert Classic. 'But I am also swinging the club very well just now and hitting lots of good shots, so maybe I am walking a half an inch taller.'
Donald, who also made his Ryder Cup debut at Oakland Hills, also played the back nine of St. Andrews first. He opened with back-to-back pars then converted a birdie try at the 12th. The Englishman made it two in a row as he birdied the 13th.
Donald, who has won twice this year in Europe, faltered to a bogey on 15, but erased that error with a birdie at the 16th. Around the turn, he picked up birdies at the first and third to get to minus-10.
The 26-year-old drained a birdie on No. 5. Donald came back with birdies at six and seven to get to minus-13. He closed with a pair of pars.
'I'm very pleased with where I am in the tournament,' Donald said. 'I've not played that well in links golf in the past, and I think I've taken full advantage of the generous conditions the last two days. I'm very happy with the way I've played. You have your amateur partners to play with and chat with and give them lines and all that kind of stuff. It takes your mind off the serious stuff and you just learn to relax and enjoy yourself out there.'
European Ryder Cup star Colin Montgomerie carded a 5-under 67 to get to 9-under-par 135. Adam Scott (67) and Angel Cabrera (66) stand alongside Montgomerie at minus-9.
Els is joined one stroke further back by defending champion Lee Westwood, former PGA Champion Rich Beem, former Masters winner Fred Couples, European Ryder Cupper Ian Poulter, as well as Stephen Gallacher, Richard Green, Peter Lonard and Rolf Muntz.