He stands alongside Peter Hanson atop the leaderboard at The Belfry, which hosted the 2002 Ryder Cup.
Defending U.S. Open champion Michael Campbell carded a 5-under-par 67 in the opening round to share third place with Paul Casey and Jarmo Sandelin, who each have won five times on the European Tour.
Clarke last played three weeks ago at the Houston Open in the United States. He withdrew after shooting 68 in the first round, which was good for a tie for fourth place, to be with his ailing wife, Heather.
The Ulsterman's wife has been battling cancer for several years and Clarke has cut back his schedule the last few years to spend more time with her.
Clarke opened his round on the back nine at The Belfry. He stumbled out of the gate with a bogey on No. 10, but Clarke atoned for that error with a birdie on the par-3 12th.
The 37-year-old came right back with a birdie 13. Clarke took advantage of 15 and 17, both par-5s, as he birdied each hole to get to minus-3. However, he tripped to a bogey at the 18th to turn at 2 under.
Clarke, an 11-time winner on the European Tour, dropped in a birdie on the par-4 second. He eagled the par-5 third to jump to minus-5. Clarke parred the next five holes before sinking a birdie on the ninth to grab a share of the lead.
'The last thing I expected was that round after the way I played Wednesday,' Clarke admitted. 'I went to the range after the Pro-Am and it was a case of either staying on the range and breaking a few clubs, or having a rest and coming back later.
'I chose the second one and went back to the range at six o'clock and worked for a couple of hours and managed to find something that semi-worked.'
Hanson, who collected his first tour win last year at the Open de Espana, got off to a hot start. He birdied the second and third, then made it three straight with a birdie on the par-4 fourth.
The Swede kept rolling as he also birdied No. 5. Hanson made it five straight as his birdie at the sixth found the bottom of the cup.
'It is amazing when things like that happen,' Hanson said of his birdie streak. 'I wasn't really knocking the shots stiff, but I was just rolling in one putt after another. It felt like the hole was so big.'
Hanson gave one stroke back to par with a bogey on eight. He parred his next six holes.
The 28-year-old moved back to 5 under thanks to a birdie at the 15th. He came right back to birdie the 16th. Hanson moved out in front at 7 under with a short birdie putt on 17. However, he three-putted for bogey at the last to drop back into a share of the lead at minus-6.
Ian Poulter, a two-time runner-up at this event, opened with a 4-under-par 68. He stands in a tie for sixth with Oliver Wilson, Andrew Coltart, Johan Edfors, Gary Emerson, David Higgins and Soren Kjeldsen. European Ryder Cup captain Ian Woosnam leads a group of 11 players one stroke further back at minus-3.
Defending champion Thomas Bjorn struggled in round one. He is tied for 120th place at 3-over-par 75 after carding a double-bogey, two birdies and three bogeys.