Mr Khan, leader of the Pakistan Movement for Justice party (PTI), has campaigned vociferously for an end to the controversial US campaign of missile strikes against suspected Taliban and Al Qaeda militants in Pakistan's tribal areas.
He argues they are illegal and counterproductive and earlier this month he led thousands of supporters - and a group of American peace activists - on a march to the edge of the restive tribal districts to protest against drones.
Mr Khan, who was headed to New York, said he was stopped by US officials in Toronto on Friday.
"I was taken off from plane and interrogated by US Immigration in Canada on my views on drones. My stance is known. Drone attacks must stop," he wrote on Twitter.
Mr Khan, led a two-day protest march earlier this month against US drone strike with some 15,000 of his supporters and dozens of Western peace activists to Tank, the last town before the semi-autonomous tribal belt.
It was an unprecedented gesture from a mainstream politician in one of the most dangerous parts of the country, a semi-autonomous zone that is a hotbed of activity by Taliban and Al Qaeda militants.
Authorities did not allow the protesters to enter the tribal district of South Waziristan - where missiles fired by US drones routinely target militants - for security reasons and blocked the road to Tank with shipping containers.
Mr Khan said the delay meant he missed his flight and a party fundraising lunch in New York, but insisted "nothing will change my stance".
"My stand on drones is very clear. I did not say sorry to them," Mr Khan told GEO news channel.
Ali Zaidi, a senior party leader demanded "a prompt and thorough inquiry into this sordid episode" and sought "an unconditional apology from the US government".
Islamist militants have killed thousands of people in Pakistan since 2007, and US officials say the drone strikes are a key weapon in the war on terror.
But peace campaigners condemn them as a breach of international law, Pakistanis as a violation of sovereignty that breeds extremism, and politicians including Khan as a sign of a government complicit in killing its own people.
Mr Khan, who is campaigning ahead of general elections next year, has made opposition to the drone programme a key plank of his party's policy.
Critics accuse him of merely trying to further his own career and of ignoring both atrocities blamed on Islamist militants and abuses by the Pakistani army.
Although leaked US cables have revealed tacit support for the drone strikes from Pakistan's military and civilian leaders, Islamabad has increasingly condemned the programme as relations with Washington have deteriorated.