If Williams can get past a qualifier in her first round match she will then face either Tokyo Olympics gold medalist Belinda Bencic or former world number one and two-time Grand Slam winner Victoria Azarenka in the second round.
Williams' brutal quarter of the draw released on Friday also includes current world number one Iga Swiatek, four-time major champion Naomi Osaka, and Canadian teen sensation Leylah Fernandez.
A three-time winner of the event and a finalist as recently as 2019, she will be unseeded this time around.
The American, who turns 41 next month, returned to action after a year away from the court at Wimbledon in June, where she suffered her second straight first round exit at the grass court major which she has won seven times. She lost a three set thriller against Harmony Tan.
The main draw of the National Bank Open in Toronto begins on August 8th and Williams is then expected to compete at the Western and Southern Open in Cincinnati before heading to New York for the U.S. Open, which begins on August 29th.