Howell carded seven birdies and an eagle for an 8-under-par 64 on the Jack Nicklaus-designed Muirfield Village course. He led Kenny Perry, last week's Colonial champion, by one stroke, while course record-holder John Huston was two behind.
As well as Howell played, it was his lone bogey, at the par-four sixth hole, that he rated as the key to his lowest round of the year. He found the water in front of the green with his second shot, but after taking a penalty stroke, got up-and-down from 100 yards to avoid dropping two strokes.
"The biggest thing that kept me going was that up-and-down. That was really important," Howell said.
He reached the turn at 2-over, before coming home in 30 strokes, including an eagle at the par-five 15th, where he hit a 4-iron to 15 feet.
Howell, who finished tied 60th at the Byron Nelson Championship before taking last week off, admitted to being a little nervous on the first tee.
Woods, meanwhile, was quite happy with his round
"It's nice to get off to a positive start like this," he said. "Scores are so low because of the perfect conditions. This is a marathon, not a sprint, and I need to keep plugging along."