Still riding the wave of the tournament record-tying 64 she fired in the first round, Stanford stands at 13-under-par 203 heading into the final round Sunday.
The only other time Stanford led after 54 holes was at the Franklin American Mortgage Championship in April, where she tied for second behind Cristie Kerr.
Her only career victory came three years ago when she went wire-to-wire at the 2003 ShopRite LPGA Classic.
She has led following all three rounds this week.
'The big thing for me tomorrow is I just need to attack this golf course,' said Stanford, who had five birdies and two bogeys Saturday. 'I have got to be aggressive.'
Aggressive shots yielded Stanford several of her birdies on Saturday, but the first two came on putts of 20 and 30 feet at the third and fifth holes.
She chipped to within 6 feet to set up a birdie at No. 7, then knocked a pitching wedge to 3 feet at the 11th to set up another birdie and reach 14 under par.
Trouble loomed for Stanford at the next two holes, however, when she made back-to-back bogeys.
At the par-4 12th, Stanford three-putted from 25 feet for a five. And on the par-3 13th, her tee shot landed in a greenside bunker and she missed a 7-foot par putt.
She managed to recover one of those shots with a birdie at the 16th, where she chipped within 2 feet of the hole.
Her biggest problem this week, Stanford said, has been her tendency to play conservatively.
'I don't know if my mind and my body just go into scared mode or I don't know what's going on, but all I know is I've got to swing at it and I've got to go aggressive,' she said.
Especially with the young Lee on her heels.
Lee, a rookie when she won here last year, carded six birdies Saturday in a bogey-free round -- half of them on putts within 4 feet. If she has a similar day Sunday, the young Korean could become the first repeat champion in this event's brief six-year history.
'Obviously I won the tournament last year, and obviously I want to defend my title here at the Canadian Open, but winning doesn't just come because I want it to,' Lee said through a translator. 'Obviously I have to play one more good round of golf tomorrow and then we'll see what happens.'
Jee Young Lee had a 71 and is alone in third place at minus-8, while Pat Hurst is one shot further back in fourth following a 70.
Lorie Kane shot a 73 on Saturday, but remained the top Canadian in the field. She is tied for fifth place with Young Kim (67), Nicole Castrale (69) and Kerr, who stumbled to a 74.