Harrington, who was named as a replacement for injured British Open champion Ernie Els over the weekend, carded seven birdies against a pair of bogeys at the Port Royal Golf Course. A three-time major winner, the Irishman last played in this exclusive event in 2008, when he lost in a playoff to Jim Furyk.
Harrington leads by two shots over Masters winner Bubba Watson, who opened with a 3-under 68 Tuesday. The leader by one shot after nine holes, Watson had the most adventurous round of the four-man field, recording an eagle and five birdies to go against four bogeys.
'It was nice to get off to a good start,' Harrington said. 'I had a 15-footer at the third and kind of lost my focus a bit on the line and drove it through the line and then hit a bad putt coming back, a terrible bogey. I wasn't feeling great. You need to be making the birdies at that stage.'
U.S. Open champion Webb Simpson finds himself in third place after a 2-under 69 in his opening round, three shots off the pace set by Harrington. In contrast to Watson, Simpson began his day with six consecutive pars before making four birdies, with his lone bogeys coming on the final hole of each side.
Defending Grand Slam champion Keegan Bradley had a rough start to his round but battled back, ultimately shooting a 1-over 72. A replacement for PGA champion Rory McIlroy, who is in Shanghai this week for the BMW Masters, Bradley played his first six holes in 4 over before birdieing three of the next four holes to help salvage his round.
'I've been six shots back before with less time, so I look forward to going out tomorrow and just making a million birdies and having a good time,' Bradley said. 'I played very well. I could have really let it slip away and fought back and had a bunch of lip-outs too, and the round could have been better than it was.'
The 36-hole exhibition will conclude Wednesday from Southampton, Bermuda, with the winner taking home $600,000 from a $1.35 million prize purse.
The Associated Press contributed to this report.