The 15-year-old South Korea-born New Zealander finished with a five-under-par 67 to win by three shots.
She broke the age record of 16, set by Lexi Thompson in the Navistar LPGA Classic in Alabama last September.
Only four other amateurs have ever won on the Tour, and Ko became the first since JoAnne Carner took the 1969 Burdine's Invitational tournament.
In January, Ko won the New South Wales Open in Australia at 14 to become the youngest player to win a professional tour event, a mark broken by 14-year-old Brooke Henderson in June in a Canadian Women's Tour event in Quebec.
Ko also won the US Women's Amateur two weeks ago in Cleveland, Ohio.
Starting the final round at The Vancouver Golf Club one shot clear, she surged away from the field on the backward nine, shooting five birdies in six holes to finish at 13 under.
Inbee Park shot a 69 to finish second on 10 under, while US Women's Open champion Na Yeon Choi, Chella Choi and Jiyai Shin tied for third at eight under.
Lydia Ko won the Canadian Women's Open to become the youngest tournament winner in LPGA Tour history.