Two convoys are taking thousands of anti-government protesters from the Pakistani city of Lahore to Islamabad, the capital, amid tight security.
The protesters are separately led by opposition politician Imran Khan and anti-government cleric Tahirul Qadri.
They want PM Nawaz Sharif to resign and have promised a change of government.
Both camps are angry about the sinking economy, growing militancy, and failure to deliver core services such as a steady electricity supply.
Mr Khan has also accused Mr Sharif of failing to probe fraud in last year's polls.
The two leaders and their followers are expected to travel 350km (218 miles) with cars, trucks, motorbikes and jeeps, says the BBC's M Ilyas Khan.
However, the convoys were making slow progress and had yet to leave Lahore as night fell on Thursday. A Reuters reporter estimated that a total of 17,000 people had turned up in support of Mr Khan and Mr Qadri.
The leaders are expected to arrive at Islamabad to stage their rallies by early Friday at the latest.
Mr Khan and Mr Qadri have agreed to assemble at Islamabad's Zero Point, a sprawling avenue at the east end of the capital, away from residential and commercial centres and the red zone, which houses government establishments and foreign missions.
Access to many main roads in Islamabad has been sealed off by riot police and shipping containers.
The government says the protesters are trying to derail democracy. But it also announced on Tuesday that a Supreme Court commission would investigate allegations of rigging in the 2013 poll.
This was dismissed by Mr Khan, who said he would only call off the march if Mr Sharif resigned.
The BBC's Shahzeb Jillani in Islamabad says the stand-off is seen as the biggest challenge yet to Mr Sharif's government.
There is anxiety and uncertainty about what will happen on the streets of the capital later, our correspondent adds.
Mobile phones jammed
Tens of thousands of security personnel have been deployed in Islamabad and in cities across Punjab province. The mobile phone network has also been partially suspended.
Many fear clashes between police and Mr Qadri's followers, who want to hold their own "revolution march" on Islamabad.
In a country with a history of military coups, there is a fear of violence and of a possible army reaction, correspondents say.
Last week at least six people were killed in Punjab province in clashes between police and supporters of Mr Qadri.
Mr Qadri, who until recently was based in Canada, returned to Pakistan in June and is one of its most prominent political and religious figures.
He leads the Pakistan Awami Tehreek (PAT) party and has condemned Mr Sharif as corrupt.
Mr Qadri has called for a military-backed government to take over from Mr Sharif, but has denied being supported by the army.