The former U.S. Open champion, fresh off a runner-up finish in Los Cabos, Mexico, was due to face Dutchman Robert Haase but has been replaced by Russian lucky loser Mikhail Youzhny.
"Sorry to my fans in Toronto, but I have to pull out of the tournament since my left wrist needs some days of rest," third seed Del Potro said on Twitter.
The 29-year-old Del Potro's career has been plagued by injuries and he missed significant time in 2014 after undergoing surgery on his left wrist.
But things were looking up in 2018 as he put together one of his best starts to a season in years as he finished runner-up in New Zealand, triumphed in Acapulco and beat Roger Federer in the final at Indian Wells.
At the French Open, he lost in the semi-finals to eventual champion Rafael Nadal, who also ended his Wimbledon run in the quarter-finals.
(Reporting by Frank Pingue, editing by Ed Osmond)
