Supporters of Khan's party, the Pakistan Tehreek-e-Insaf (PTI), clashed with police in the city of Lahore last week as they attempted to arrest him at his home, and later with police in Islamabad as he arrived to appear before a court on Saturday.
"Around 285 PTI supporters have been arrested in Lahore and Islamabad. Houses of all major leaders were raided by police last night," Khan's aide, Fawad Chaudhry, told Reuters.
Khan, a former cricket star, was prime minister from 2018 until 2022, when he was ousted from office in a parliamentary vote.
Since then he has been demanding a snap election and holding protest rallies across the country to press his case.
His successor as prime minister, Shehbaz Sharif, has rejected his demand and said an election would be held as scheduled later this year.
Khan, 70, is facing several legal cases, including one that prompted a failed attempt to arrest him on Tuesday after a court issued warrants for his arrest for failing to appear.
Clashes between Khan's supporters and the security forces have brought a new round of political chaos to Pakistan, which is in the midst of a crippling economic crisis.
Khan says the government and the powerful military are trying to stop him from contesting the next election, scheduled for November.
If convicted in a case, Khan could face disqualification from the polls.
Both the government and military deny this.
Police in both Lahore and Islamabad confirmed the raids and the arrest of PTI workers they said were involved in clashes with police and arson.
"Police are raiding the houses because seven cases on various charges, including terrorism, have been registered against the leaders and workers," Lahore police chief Bilal Kamiana told Reuters referring to the clashes with police.
He said 125 activists had been arrested in Lahore, including some last week.
In Islamabad, a police spokesman said 198 PTI supporters had been arrested in connection with arson and attacks on police in which 58 people were injured and more than a dozen vehicles, including some police cars, were set ablaze.
More raids were being carried out, the spokesman said.
He said police had also gone to the home of a sitting PTI senator, Shibli Faraz, with a search warrant, but the senator was not home.
Khan, remembered by many for his success as a cricket player and later for his charity work, won considerable support among sections of the electorate with his conservative, nationalistic policies.
