Pakistan Muslim League-Nawaz party members Asif Kirmani and Captain Safdar filed the nomination papers of Kulsoom, who is in her late 60s, for the upcoming by-poll for the NA-120 seat at the Election Commission of Pakistan's (ECP) Lahore office, Dawn News reported.
"NA-120 will prove to be Waterloo for (Pakistan Tehreeki-Insaf chief) Imran Khan and other opponents of Nawaz Sharif," Kirmani was quoted as saying by the report.
The National Assembly seat fell vacant after 67-year-old Sharif was disqualified by the Supreme Court in the Panamagate case on July 28.
The former prime minister had earlier announced his younger brother Shahbaz Sharif's name as the party candidate.
His name was later withdrawn as party members deemed his presence in Punjab too important.
"Nawaz Sharif has made a smart move. By fielding his wife in the by-poll he has planned to move to the prime minister house again and this time in the capacity of 'first gentleman' next month," a senior PML-N leader who is close to the Sharif family told PTI.
He said after winning the election on September 17 Prime Minister Shahid Khaqan Abbasi will leave the top post for Begum Kulsoom.
Pakistan Tehreek-i-Insaf's candidate Dr Yasmin Rashid also submitted her nomination papers in the morning.
When asked about Kulsoom's candidacy, Rashid said that the difference between them is that she is a "hardworking middle-class woman who will represent the ordinary people of the country," whereas Kulsoom comes from what her daughter, Maryam Nawaz, has called the "ruling family."
Rashid further said that the PML-N was being "forced" to contest the by-election due to Nawaz's ouster, adding that they should do so on a level playing field without using government machinery.
Kulsoom had successfully led the party's movement for the release of her incarcerated husband after a military coup by former president Parvez Musharraf in 1999.