Canadians also can order marijuana products through websites run by provinces or private retailers and have it delivered to their homes by mail.
Alberta and Quebec have set the minimum age for purchase at 18, while others have made it 19.
No stores will open in Ontario, which includes Toronto. The most populous province is working on its regulations and doesn't expect stores until next spring.
Ryan Bose, 48, a Lyft driver in Toronto, said it's about time.
"Alcohol took my grandfather and it took his youngest son, and weed has taken no one from me ever," he said.
A patchwork of regulations has spread in Canada as each province takes its own approach within the framework set out by the federal government. Some are operating government-run stores, some are allowing private retailers, some both.
Canada's national approach has allowed for unfettered industry banking, inter-province shipments of cannabis and billions of dollars in investment — a sharp contrast with national prohibition in the United States.
Nine U.S. states have legalized recreational use of pot, and more than 30 have approved medical marijuana. California, the largest legal market in the U.S., earlier this month became the first state with a law mandating expungement of criminal convictions for marijuana-related offenses that no are longer illegal.
Democratic Sen. Ron Wyden of Oregon said it's time for the U.S. government to follow Canada's lead.
"Now that our neighbor to the north is opening its legal cannabis market, the longer we delay, the longer we miss out on potentially significant economic opportunities for Oregon and other states across the country," he said in a statement.
U.S. Customs and Border Protection invited Canadian media to a conference call on Tuesday so officials could reiterate that marijuana remains illegal under U.S. federal law and that those who are caught at the border with pot are subject to arrest and prosecution.
As Canada welcomes legalization, supply shortages could develop, as happened in some U.S. states when legalization arrived.
Trevor Fencott, chief executive of Fire and Flower, said his company has 15 Alberta stores staffed and ready to sell marijuana, but the province has supplied only enough product to open three of them Wednesday.
"We're aware of some of the kinks or growing pains that come with creating an industry out of whole cloth in 24 months," Fencott said.
Brenda Tobin and her son Trevor plan to open their pot shop in Labrador City in Newfoundland and Labrador at 4:20 p.m. Wednesday — 420 is slang for the consumption of cannabis. Tobin, a longtime convenience store owner, said they will be cutting a ribbon and cake.
"We are just ecstatic," she said.
She doesn't expect to make much money off the pot itself, noting Newfoundland's 8 percent cap on retail pot profits. She hopes to make money from pipes, bongs and marijuana paraphernalia.
"There's no money in the product itself," she said. "You got to sell $250,000 worth of product in order to make $20,000. That's not even paying someone's salary."