Hedwall, who went 5-0 to help Europe beat the United States last week, fired a round of six-under 64 to edge one shot clear of Suzann Pettersen and defending champion Lydia Ko.
Hedwall, who had back-to-back rounds of 68 on the opening days in Edmonton, had seven birdies and one bogey in her round of 64.
And that was enough to leave her clear at the top as Pettersen fired a 65 and Ko a 67.
Brittany Lincicome and IK Kim were in a share of fourth place, two shots back.
World number one Inbee Park had moved to the top of the leaderboard on Friday with a round of 65 but suffered a complete reversal a day later, with three bogeys and a double bogey on the 11th leading to a round of 74 that sent her plummeting to a share of 15th.