The 20-year-old from Markham, Ont., won in a personal-best 9.95 seconds, becoming the first person to run a sub-10 on Canadian soil since Maurice Greene, who ran 9.82 at the 2001 world championships in Edmonton.
Toronto's Aaron Brown was second in 10.13, while Justyn Warner, also of Toronto, was third in 10.16 seconds.
De Grasse, a junior for the University of Southern California, stunned the track world when he won both the 100 and 200 races — less than 45 minutes apart — at the recent NCAA championships.
He ran 9.75 in the 100 and 19.58 in the 200 metres in Eugene, Ore., but both times were slightly over the allowable wind of 2.0 metres per second.
Also, Khamica Bingham of Brampton, Ont., edged out the women's 100 competition in 11.19.
Matthew Hughes captured the men's 3,000 steeplechase in 8:31.95. The Oshawa, Ont., native beat Alex Genest and Taylor Milne, who finished second and third respectively.
Winnipeg's Erin Teschuk won the women's 3,000 steeplechase in 9:54.18. Genevieve Lalonde was second and Julie-Anne Staehli narrowed placed third.
Christabel Nettey of Surrey, B.C., won the women's long jump event while Vancouver's Elizabeth Gleadle placed first in the women's javelin throw. Caleb Jones of Saint John, N.B., won the men's javelin.
Quinn Erickson had the longest toss in the women's discus throw with 48.49 metres.