Harrington and Ian Poulter last played the BMW PGA Championship three years ago, but both are back this year to compete at the redesigned Surrey course.
Harrington was out in a superb 32 as the Dubliner, without a European Tour victory since capturing his third Major title at the 2008 US PGA Championship, birdied the third, fourth and sixth to be alongside playing partner and Ryder Cup teammate Søren Hansen.
First prize this week is €750,000 and Hansen, no relation to double Wentworth winner Anders, matched Harrington shot for shot on the front nine.
They were then joined on three under by England's Danny Willett and also South African Ernie Els, who played a key role in deciding the changes to the course.
Most eye-catching is the introduction of water in front of the green at the par five 18th, but with that still to come Els, seven times the winner of the World Match Play on the course, had a hat-trick of birdies from the eighth.
One stroke behind were Wentworth scholarship graduate Ross Fisher, runner-up to Paul Casey after a dazzling closing 64 last May, Essex's Oliver Fisher, Welshman Rhys Davies, Swede Peter Hedblom and Anders Hansen.
Davies, making his debut in the event after winning the Hassan II Trophee in Morocco two months ago, bogeyed the third, but hit back with birdies on the fourth, seventh and eighth.
Willett, a Walker Cup teammate of Rory McIlroy in 2007, then made it three birdies in a row on the eighth.
Søren Hansen reached four under as well with a 20 footer at the 11th, but could not get up and down from sand at the next - now a tough par four rather than a par five - and slipped back to joint second spot with Harrington and Els.
Scot Marc Warren was the first player to hole out on the new 18th - and it was for an eagle.
Six over par at the time, he alone of the opening group decided to go for the green, hit a four iron to 15 feet and made the putt.
Willett, meanwhile, bogeyed the 11th after straying into sand with his approach and fell into a seven-way tie for the lead.
Also three under were Els, Harrington, Scots Stephen Gallacher and Scott Drummond, Australian left-hander Richard Green and Chinese Taipei's Lin Wen-tang.
Hansen, though, had another bogey at the 13th and dropped two more at the 179 yard 14th after thinning a bunker shot completely over the green.
Ross and Oliver Fisher both had their troubles, the former double bogeying the 13th after driving deep into the trees and taking a penalty drop and the latter on the eighth.
|T2||ANDERSSON HED, Fredrik||SWE||18||-5|