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TV footage showed police slowly approaching the Zaman Park residence of Khan behind an armoured vehicle that was dispersing his supporters with a water cannon.
A senior police officer of Islamabad police said that his team has come here to arrest the Pakistan Tehreek-e-Insaf (PTI) chairman in the Toshakhana case.
Khan has been in the crosshairs for buying gifts, including an expensive Graff wristwatch he had received as the premier at a discounted price from the state depository called Toshakhana and selling them for profit.
Clashes erupted between police and PTI workers when the former approached Khan's residence to arrest him. His supporters, who had covered their faces with pieces of cloth, pelted stones at policemen resulting in injuries.
According to reports, Islamabad Deputy Inspector General (Operations) Shahzad Bukhari, who was leading the police team, was injured. He was seen walking with the help of two officials. Both Khan's supporters and policemen were injured in the clashes.
In a video message, Khan urged his supporters to come out for real freedom as police had arrived to arrest him. "They think that after my arrest, the nation will fall asleep. You have to prove them wrong," Khan said in the video.
"If something happens to me and I am sent to jail or if I am killed, you have to prove that you will struggle without Imran Khan and not accept the slavery of these thieves and of the one person who has been making decisions for the country," he said.
PTI leader Shireen Mazari shared a video in which tear gas could be seen entering Khan's residence.
"They're shelling Imran Khan's house too, a leader who requested everyone to stay peaceful and patient. Democracy seems to be suspended in the country, no?" the official Twitter handle of the party tweeted.
Meanwhile, the party's deputy leader Shah Mahmood Qureshi said that the PTI leadership is ready to find out a "possible way out" to avert bloodshed.
"Show me the warrant. I will first read and understand it. Then, I will speak to Imran Khan and my lawyers," he told the police.
Former information minister Fawad Chaudhry said that the party leaders have moved the Islamabad High Court against the arrest warrants issued in the Toshakhana case.
The official Twitter handle of the party earlier urged supporters and workers to gather outside the residence and 'remain peaceful'.
A large number of PTI workers equipped with clubs were present outside the 70-year-old leader's residence to resist the police action.
The police blocked all roads leading to the house of the PTI chairman by placing containers and riot personnel took positions to launch the operation.
Senior PTI leader Farukh Habib told reporters that come what may Imran Khan would not surrender to police in fake cases. "The arrest warrants in the case related to threatening a female judge were today suspended by the Islamabad High Court. Let's see what new warrants police have brought with them now," Habib said.
One activist of Khan's party was killed on Wednesday during a crackdown on his supporters who gathered outside his residence in Lahore, defying a government ban on rallies in the city.
On Monday, the Lahore police had booked Khan in a case related to the killing of the PTI worker - Ali Bilal alias Zille Shah - in a road accident.
Earlier, the Lahore police had registered an FIR against Khan and 400 others for the murder of Shah. "The new FIR has been registered against Imran Khan, Fawad Chaudhry, Dr Yasmin Rashid and a number of other PTI men for abetment to murder, concealing facts and evidence related to the death of Zille Shah," a senior police officer told PTI.
He said the police may arrest Khan and others nominated in the FIR after direction from the "top". The PTI had accused the police of murder of Shah after inflicting brutal torture on March 8.
This is the 81th FIR against Khan since the PML-N led federal coalition came into power 11 months ago after toppling his government through a no-confidence motion.
Khan Monday led a march of thousands of his supporters, a day after he called off his party's election rally following a ban on public gatherings in Punjab's provincial capital.
The former cricketer-turned-politician's supporters threw rose petals at a convoy carrying him to Data Darbar shrine.
Khan was ousted from power in April last year after losing a no-confidence vote, which he alleged was part of a US-led conspiracy targeting him because of his independent foreign policy decisions on Russia, China and Afghanistan.
Since his ouster, Khan has been clamouring for immediate elections to oust what he termed an "imported government" led by prime minister Shehbaz Sharif.
Sharif has maintained that elections will be held later this year once the parliament completes its five-year tenure.