Monday's vote is not a direct referendum on independence; rather, Alberta, which has the world's fourth-largest proven oil reserves, will decide whether to remain a province or instruct the government to begin the legal process towards a referendum on separation.
"This referendum comes at the worst possible time," Carney told a pro-Canada rally in Calgary on Thursday.
"The world has become more dangerous and divided. Some outside our borders are working to break us so they can own us."
He did not directly mention the US or its President Donald Trump, but has done so in similar past speeches.
Carney's warning came amid US President Donald Trump's trade war with Canada and repeated threats to make Canada the 51st US state.
Carney has argued that Canada needs to become more economically resilient and less dependent on the United States.
Carney urged Albertans not to use the vote simply to send Ottawa a message, saying a decisive result could settle the separation question.
"This is not poker. A vote against Canada is a dangerous bluff that will lead to years of deep division and great uncertainty," he said.
Carney, who grew up in Alberta, spent Thursday campaigning in Calgary before addressing a Forever Canadian rally.
Organisers are holding a second rally with Carney in Edmonton on Friday.
At the rally, Carney acknowledged the grievances that had fuelled alienation in Alberta.
"The frustrations that many Albertans have felt are real," he said.
Carney said that while growing up, Ottawa made Albertans feel "like our resources weren't our own" and that more recently the province was made to feel its energy contributions were "against the tides of history".
The setting is striking for a Liberal prime minister.
Alberta has spent decades feuding with Liberal governments in Ottawa, particularly over energy and federal power.
But Carney has broken with some of the policies associated with his predecessor, Justin Trudeau, fast-tracked a proposed new oil pipeline to the Pacific and called Canada an energy superpower.
Carney pointed to the Pacific Link pipeline as evidence of a changed relationship, saying it would create more than 140,000 jobs, reduce Canada's dependence on the United States and generate revenue for social programs.
Tanya Clemens, co-chair of the pro-independence group Let Alberta Decide, acknowledged Carney presented a challenge.
"He's formidable for sure," Clemens told The Associated Press.
Clemens argued, however, that Carney's agreements with Alberta Premier Danielle Smith amounted to "pinky promises" that did not resolve long-standing grievances with Ottawa.
Advance voting runs through Saturday, with the final vote on Monday.
