However, the PML-N could reap a sympathy vote after Nawaz Sharif returned to be arrested on July 13 along with his daughter Maryam, leaving his cancer-stricken wife in a London hospital.
Imran Khan, Tehreek-e-Insaf party leader, addresses the crowd ahead of Wednesday's election.
Shehbaz Sharif, leader of the Pakistan Muslim League-Nawaz and brother of the ousted prime minister, early on Thursday rejected the counting process as results were still trickling out and no victor had been declared but projections showed a strong lead for Khan.
The poll panel has sent Khan a notice.
The Pakistan Peoples Party (PPP) of former president Asif Ali Zardari was leading on 26 seats, possibly giving him a chance to play kingmaker in case of a hung parliament.
Voting began at 8 am (local time), during which most of Pakistan's almost 106 million people came out to cast their votes. More than 30 political parties have fielded their candidates for the elections.
Polling took place in the country's 85,307 polling stations, out of which 17,007 were declared as "highly sensitive".
For the first time in 2013, a civilian government in Pakistan completed its five-year term.
But campaigning has been plagued by allegations the powerful armed forces have been trying to tilt the race in Khan's favor after falling out with the outgoing ruling party of Sharif, who was jailed on corruption charges this month.
Khan cast his vote in Bani Gala, a suburb of the capital Islamabad, telling the media it was "time to defeat parties which kept this country hostage for years".
Whichever party wins, it will face a mounting and urgent in-tray, from a brewing economic crisis to worsening relations with on-off ally the United States to deepening cross-country water shortages.More news: Oil jumps after Trump warns Iran of grave 'consequences'
An anti-corruption crusader, Khan has promised an "Islamic welfare state" and cast his populist campaign as a battle to topple a predatory political elite hindering development in the impoverished mostly-Muslim nation of 208 million people, where the illiteracy rate hovers above 40 percent.
"I ask everyone today - be a citizen, cherish this country, worry about this country, use your vote".
The MQM-P also expressed similar concerns in a news conference in Karachi, in which Faisal Sabzwari claimed that their polling agents were not being provided certified copies of the election results by the ECP in Hyderabad and Karachi.
But while several polls put Khan's Pakistan Tehreek-e-Insaf (PTI, or Pakistan Justice Movement) marginally ahead - the result, his rivals allege, of covert support from the country's powerful military establishment - other surveys suggest the result is too close to call.
Khan has staunchly denied allegations by PML-N that he is getting help from the military, which has ruled Pakistan for about half of its history and still sets key security and foreign policy in the nuclear-armed nation.
Elsewhere, anger with the alleged conspiracy to unseat the PML-N was apparent among some voters.
All the mainstream political parties have raised serious reservations over the credibility of the polling process.
In the western city of Quetta, at least 31 people were killed and dozens more injured in a Daesh suicide attack outside a polling station, police and local media reported Wednesday.
Sharif has denied any wrongdoing and accused elements of the judiciary and military of conspiring to bring down his government.
It was the second major attack by Daesh this month in Balochistan province after an earlier blast at a campaign rally killed 153.
However, the day has not been without violence, as interparty violence and militant attacks have left over a dozen dead.