Emily Bastel carded a 5-under-par 67 to take second place and Linda Ishii was one stroke further back at minus-4 at Glen Arbour Golf Course.
Moodie got her round going with a 12-foot birdie putt on the par-3 second and made it two straight with a 5-foot birdie putt on three.
The 32-year-old ran home a 45-footer for birdie at the fourth and made it four in a row when she kicked in a 3-foot birdie try on No. 5.
Moodie, a two-time winner on tour, made the turn at minus-5 thanks to a birdie at the ninth. She reeled off eight straight pars from the 10th and then drained a 15-foot birdie try at the last to close a bogey-free round.
'To be honest with you, I had a couple of good up and downs for par towards the middle part there when the wind got a little bit swirly,' said Moodie. 'So making pars was good. Then the birdie at the last and not making any bogeys was key.'
Bastel stumbled out of the gate with a bogey at the first, but erased that mistake with a birdie on the par-4 eighth.
Around the turn, the 24-year-old sank a 25-foot birdie try on the 11th. Bastel then aced the par-3 13th as her 7-iron tee shot rolled into the cup get her to minus-3.
Bastel got up and down for birdie on the 14th and moved within one stroke of the lead with a birdie from 8 feet out on the 15th. She then parred her final three holes to remain there.
'It was a little exciting, definitely,' said Bastel. 'After I hit the poor shot on one, I pretty much kept it in play with a the driver after that. And then after the hole in one, it was just the momentum that helped me make those other birdies.'
Il Mi Chung, Johanna Head, Cathy Johnston-Forbes, Brittany Lang, Mhairi McKay, Angela Stanford and Sherri Turner share fourth place at 3-under-par 69.
Meg Mallon, who last year became the first person to win this crown after also winning the U.S. Women's Open, opened with a round of 2-under-par 70. She stands in a tie for 11th place alongside Beth Bader, Audra Burks, Jen Hanna, Diana D'Alessio, Christina Kim, Shani Waugh, Karen Weiss, Young-A Yang and Naree Song.