A 3-under 68 gave the defending champion a seven-under total of 135 at the venue for last year’s Ryder Cup, one behind Alexander Noren of Sweden (67).
McDowell cracked a 385-yard drive at the 18th hole to set up his fifth birdie of the day.
“I can’t remember hitting the ball any longer than that,” the Briton told reporters at the course where he recorded the winning Ryder Cup point for Europe in October.
Last year McDowell was six shots off the Wales Open pace going into the weekend but then carded rounds of 64 and 63 to storm to victory by three strokes.
Brimming with confidence from his win in Wales, the Northern Irishman went on to claim his first major title in the US Open at Pebble Beach.
“All I want to do this weekend is get into the mix and get some juices flowing, put the game under a bit of pressure,” said McDowell who fashioned his round on four birdies in five holes around the turn.
“Then I’ll take some great positives away with me (for this month’s US Open).”
Noren, the 2009 European Masters winner, also claimed four birdies in five holes with his run starting at the 14th.
The 28-year-old Swede said he had drastically reduced his practice this week.
“I love practising and it hurts not going to the range but after the PGA Championship last week, 36 holes for US Open qualifying on Monday and 36 to come next Monday for British Open qualifying I feel I should be relaxing and doing all my work on the course,” said Noren.
In joint third place on 136 were Briton Jamie Donaldson (68) and Frenchman Victor Dubuisson (69).
McDowell’s Ryder Cup team mate Peter Hanson of Sweden was among a trio of players three strokes off the lead that included 50-year-old Briton Barry Lane and overnight leader Keith Horne of South Africa.
Colin Montgomerie, captain of Europe’s 2010 Ryder Cup team, produced his worst two opening rounds for 20 years as he plummeted to 157, 15 over.
