Officials said officers and paramedics were called to Yonge Street beside the square before 11:10 p.m. with reports of the sounds of gunshots.
Toronto Paramedics said the victim was taken by their crews to a nearby trauma centre in critical condition.
Toronto police homicide squad Det. Stephen Henkel told reporters early Thursday the man died in hospital. The victim was later identified as Israel Edwards.
Henkel said investigators are trying to determine how many suspects might be involved and to retrace the victim’s movements before the shooting.
“There were quite a few people out last night at 11 p.m. in the square and in the surrounding area,” Henkel said.
“Any incidents involving gun play is of concern to us. And again, being in the downtown is of concern to us.”
Members of Toronto’s emergency task force were called in to assist with a ground search, Henkel said. Several plain clothes officers could also be seen at the scene early Thursday.
The incident comes after several shooting deaths in recent days.
On Monday night, 37-year-old Matthew Staikos was shot and killed while walking near Bay Street and Yorkville Avenue.
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On Sunday night, 21-year-old Venojan Suthesan was found fatally shot near Lester B. Pearson Collegiate Institute in Scarborough.
A week earlier Jaiden Jackson was gunned down on a parking ramp below a building near Yonge Street and Wellington Street West after a brief pursuit.
Toronto police spokesperson Mark Pugash addressed the recent spike in violence on Tuesday and said these types of clusters happen every year.
“Of course it’s concerning. We’re making excellent arrests. We’re taking guns off the streets and we’re putting all of our resources into solving these homicides,” he said, adding Toronto is still the safest city in North America.
“People often want simple explanations for complicated problems and there is no simple explanation … and we have some of the best homicide investigators in the country.”
Mayor John Tory released a written statement Thursday morning condemning the recent homicides.
“The incidents of gun violence we have seen in our city in the past few days are shocking and can in no way be accepted or brushed aside,” he said.
“This morning, I spoke to Chief Mark Saunders about last night’s murder and other recent acts of violence in our city. I have been assured that Toronto police are doing everything possible to bring the perpetrators of these despicable crimes to justice.”
Meanwhile, Henkel said officers are looking to speak with anyone who might have surveillance, cellphone or dash camera footage in the area from the time of the shooting.
Anyone with information is asked to call police at 416-808-7400 or 416-808-5200, or Crime Stoppers anonymously at 416-222-8477.