Stuart Appleby, who won for the second time this season at the Shell Houston Open last week, is one stroke further back at minus-7.
Phil Mickelson returned to action this week for the first time since winning his second Masters title. He started the tournament with a 4-under-par 68 and is tied for 22nd.
McDowell began his round on the back nine at English Turn Golf & Country Club. He opened with a birdie on the 10th and came back with a birdie on No. 13.
The Ulsterman posted his third birdie on the 16th and turned in minus-4 thanks to a birdie on the 18th. McDowell made it two straight as he birdied the first.
McDowell climbed to 6 under as he birdied the fourth. That birdie gave him a share of the lead. After parring the next four holes, the 26-year-old holed a wedge shot from 116 yards out for eagle on the par-4 ninth to jump to minus-8.
'Obviously, to finish with a two at the last, that was a real bonus,' McDowell stated. 'It doesn't matter how good you hit it. To get the ball in the cup takes a bit of luck. I've been waiting for this round for a while.'
Appleby, who won in wire-to-wire fashion last week, opened with a birdie on the second. The Australian picked up his next birdie on the fourth and came right back with a birdie on No. 5.
The three-time defending champion at the Mercedes Championships made it three straight as he birdied the par-5 sixth.
Appleby, who turns 35 this coming Monday, parred the next four holes then took advantage of another par five. He birdied the par-5 11th to move to 5 under.
After three straight pars, Appleby joined the logjam at minus-6 with a birdie on the par-5 15th, as he birdied all four par-5s on this day. He closed with a birdie at the last to get within one of McDowell.
Chris DiMarco, 2003 champion Steve Flesch, Cameron Beckman, David Branshaw, Tim Herron, Ryan Hietala, Ian Poulter, Jerry Smith and Darron Stiles share 13th place at 5-under-par 67.
Mickelson was joined by 16 more players at minus-4 as 38 golfers shot 4 under par or better in the opening round.
Defending champion Tim Petrovic is part of a large group of golfers tied for 81st at 1-under-par 71.