Marijuana sales began just after midnight local time in Newfoundland, its easternmost province.
Medical marijuana has been legal in Canada since 2001, and Justin Trudeau’s government has spent two years working to expand that to include recreational use.
The prime minister has said his aim is to better reflect society’s changing opinion about marijuana and bring black-market operators into a regulated system.
It comes as Canada’s former Conservative prime minister, Brian Mulroney, was appointed to the board of US cannabis company Acreage Holdings, the Financial Times reported.
He told the paper the drug “meets a need, both a medical need and a social need” and said Canada’s attitude towards marijuana “will be quite widely admired around the world”.
At least 111 legal pot shops are expected to open across the nation of 37 million people on Wednesday.
Canadians will be allowed to carry up to 30 grams of cannabis in public and will be able to grow up to four marijuana plants per household.
People can also order cannabis products through websites run by provinces or private retailers and have them delivered in the post.
Most Canadian states have set the minimum age for purchase 19, while Alberta and Quebec have made it 18.
Canadian police have told people not to report their neighbours for growing or smoking weed after the ban was lifted.
Toronto police urged people in a series of tweets not to contact officers about “your neighbour’s pot plants”, “smelling weed from your neighbour’s home”, or “an adult smoking a joint”.
“Cannabis is no longer illegal,” the posts said. “Do not call police for this.”
Uruguay was the first country to legalise marijuana in 2013, though Portugal and the Netherlands have decriminalised it.
Nine US states have legalised the recreational use of cannabis, and more than 30 have approved medical marijuana.
On Tuesday, US Customs and Border Protection reiterated that marijuana remains illegal under US federal law, and said those who are caught at the border with pot will be subject to arrest and prosecution.