Witnesses described scenes of panic after gunfire broke out in the food court of the Eaton Centre.
"A herd of people were just running toward us, screaming, running, freaking out," said one shopper.
Police said two of the injured were in a critical condition and warned that they were still hunting the shooter.
A 13-year-old boy was among those seriously injured.
Officials said a 25-year-old man was pronounced dead at the scene.
As crowds gathered outside, an injured man with two bullet wounds in his chest was wheeled out on a stretcher and rushed away by ambulance.
Toronto police chief Bill Blair described it as a targeted shooting in which bystanders were also hit.
"The nature of the wounds indicate this individual was targeted," he said.
"A lot of innocent people were hurt and a lot of innocent people were put at risk.
"We will be relentless in our pursuit of the individual or individuals that were responsible. We are receiving a lot of co-operation from the people that were present in the food court."
He added: "I believe every Torontonian is shocked and appalled by this crime."
Although some witnesses said they saw a man with a gun, Toronto Mayor Rob Ford told reporters at the scene that it was not immediately clear if the shooter was a man or a woman.
"It's terrible when you hear something like this," said Mr Ford.
"My heart goes out to the families that have been affected by this terrible crime. We have to apprehend this shooter."
Marcus Neves-Polonio, 19, who works in the shopping centre's food court, said he saw a man pull out a gun and start firing. He saw at least two people on the ground.
Erica Solmes, manager of a McDonald's outlet, said she heard about 15 shots before hundreds of shoppers started stampeding for the exits.
Police constable Victor Kwong said at least two people had been trampled in the rush, including a pregnant woman who subsequently went into labour.
Gun ownership in Canada has been subject to licensing since the 1970s, and gun crime has dramatically declined over the years.
The last similar incident in Toronto was in 2005, when a gunman opened fire in a street near to the Eaton Centre and killed a teenage girl.
Source: BBC News
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