Pakistan is one of only three countries in the world where polio remains endemic, and efforts to stamp it out have been hit by opposition from Islamist militants and attacks on vaccination teams.
Police foiled an attempted attack on a polio team in Karachi on Tuesday, while a Taliban ban on inoculation in the tribal region of North Waziristan last year has been blamed for a surge in cases.
Khan's Pakistan Tehreek-e-Insaaf party leads the government in the northwestern province of Khyber Pakhtunkhwa, which borders North Waziristan.
He said attacks on polio workers must end.
"Those who are attacking polio workers are doing injustice to our province, our country and the whole of humanity," Khan told reporters.
"If we run a full-fledged campaign against polio in the coming three months we can eradicate polio from the country and I will personally lead this campaign."
Khan kickstarted the campaign by administering polio drops to children in a government hospital in the town of Akoda Khattak, 50 km (30 miles) east of Peshawar.
He appeared alongside radical cleric Maulana Sami-ul-Haq, known as the "Father of the Taliban", who last week issued a fatwa urging parents to immunise their children against polio, saying vaccinations complied with Islamic law.
Doctor Imtiaz Khan, focal person for the polio campaign in the province, told AFP that up to 2.3 million children in nine districts would be targeted in the immunisation drive.
"As many as 52 cases of polio were reported from the tribal areas and 10 from Khyber-Pakhtunkhwa this year," he said.
According to the Global Polio Eradication Initiative led by the World Health Organisation, Pakistan has recorded 74 cases of polio this year -- up from 58 in the whole of 2012.
Imran Khan warned that people might not be allowed to travel out of the province in the near future unless the polio virus was eradicated.
Last month the World Health Organisation linked an outbreak of polio in Syria that has paralysed 13 children to a strain of the virus from Pakistan.
Earlier this month New Delhi announced it would require citizens from Pakistan and other polio-affected nations travelling to India to undergo polio vaccination at least six weeks before departure.