Protesters armed with sticks and slingshots took on police in western Islamabad, less than 10 kilometres (six miles) from the government enclave they aim to occupy.
The government said one police officer had been killed and nine were critically wounded in two days of clashes with demonstrators as they closed in on the capital.
Khan was barred from standing in February elections that were marred by allegations of rigging, sidelined by dozens of legal cases that he claims were confected to prevent his comeback.
His Pakistan Tehreek-e-Insaf (PTI) party has defied a government crackdown with regular demonstrations aiming to seize public spaces in Islamabad and other large cities.
The capital has been locked down since late Saturday, with mobile internet sporadically cut and more than 20,000 police flooding the streets, many armed with riot shields and batons.
Last week, the Islamabad city administration announced a two-month ban on public gatherings.
But PTI convoys travelled from their power base in northwestern Khyber Pakhtunkhwa province and the most populous province of Punjab, hauling aside roadblocks of stacked shipping containers.
"We are deeply frustrated with the government, they do not know how to function," 56-year-old protestor Kalat Khan told AFP on Monday. "The treatment we are receiving is unjust and cruel."
The government cited "security concerns" for the mobile internet outages, while Islamabad's schools and universities were also ordered to shut on Monday and Tuesday.
"Those who will come here will be arrested," Interior Minister Mohsin Naqvi told reporters late Monday at D-Chowk, the public square outside Islamabad's government buildings that PTI aims to occupy.
'Panic' in Islamabad
PTI's chief demand is the release of Khan, the 72-year-old charismatic former cricket star who served as premier from 2018 to 2022 and is the lodestar of their party.
They are also protesting alleged tampering in the February polls and a recent government-backed constitutional amendment giving it more power over the courts, where Khan is tangled in dozens of cases.
Prime Minister Shehbaz Sharif's government has come under increasing criticism for deploying heavy-handed measures to quash PTI's protests.
"From the scale of preparations, one wonders if the Islamabad Police is preparing for war," said an editorial in the English-language Dawn newspaper last week.
"The city administration may have intended to demonstrate strength by sharing the plans it has made, but instead, it looks like it is panicking."
The Human Rights Commission of Pakistan said "blocking access to the capital, with motorway and highway closures across Punjab and Khyber Pakhtunkhwa, has effectively penalized ordinary citizens".
The US State Department appealed for protestors to refrain from violence, while also urging authorities to "respect human rights and fundamental freedoms and to ensure respect for Pakistan's laws and constitution as they work to maintain law and order".
Khan was ousted by a no-confidence vote after falling out with the kingmaking military establishment, who analysts say engineer the rise and fall of Pakistan's politicians.
But as opposition leader he led an unprecedented campaign of defiance, with PTI street protests boiling over into unrest that the government cited as the reason for its crackdown.
PTI won more seats than any other party in this year's election but a coalition of parties considered more pliable to military influence shut them out of power.
Khan has been jailed since August 2023, facing a procession of legal accusations ranging from illegal marriage to graft and inciting riots.
