No prime minister has ever seen out a full term in Pakistan, and Khan is facing the biggest challenge to his rule since being elected in 2018, with opponents accusing him of economic mismanagement and foreign-policy bungling.
The government is also battling to contain a rise in militancy by the Tehreek-i-Taliban Pakistan (TTP).
Fighting for his political life, Khan addressed the nation, appearing to blunder when he named the United States as the origin of a "message" he said showed meddling in Pakistan's affairs.
"America has -- oh, not America but a foreign country I can't name. I mean from a foreign country, we received a message," he said.
Reports appearing in the media have said the message was in a briefing letter from Pakistan's ambassador to Washington, Asad Majeed Khan, recording a senior US official telling him they felt relations would be better if the prime minister left office.
"They say that 'our anger will vanish if Imran Khan loses this no-confidence vote'," he said.
In Washington, State Department spokesman Ned Price told reporters there was "no truth" to the allegations.
"We are closely following developments in Pakistan. We respect (and) we support Pakistan's constitutional process and the rule of law," Price said.
Khan has long complained that Pakistan was asked to sacrifice too much in joining Washington's "war on terror", launched in the aftermath of the 9/11 attacks, with too little recognition or reward.
"Has anyone said 'thank you Pakistan' for what we did?" he asked in Thursday's address.
Khan spoke off-the-cuff for around 45 minutes, touching on several topics including his efforts to get Islamophobia recognised as a global threat, and charting an independent path for Pakistan on the world stage.
-- With input from AFP
