[5] Wazir's family was long active in the Pashtun nationalist movement and opposed to the Talibanization of the former tribal areas, earning them the militants' enmity.

His father (Malik Mirzalam), two brothers (Farooq and Tariq), two uncles (Saadullah Jan and Feroz Khan), and three cousins (Ibrahim, Ishaq and Arif Wazir) were all murdered in targeted killings.

While studying law at the Gomal University, Dera Ismail Khan, he was influenced by the International Marxist Tendency (IMT) group and became a political activist.

Referring to her struggle later, Ali's mother said, "when I moved to Dera Ismail Khan in 2005, after my sons and husband were murdered, I brought 15 orphans with me.

"[4] On 1 May 2020, Ali's first cousin Arif Wazir, who had been released from jail just four days earlier, was critically injured when gunmen shot him in Wanna.

Their gas stations were demolished, their tube wells were filled with dirt, and their apple and peach orchards were sprayed with poisonous chemicals.

[20] In 2016, the government demolished their market in Wanna with dynamite under the Frontier Crimes Regulation, which authorized collective punishment, after a bomb killed an army officer.

[6] In his opinion article for The Diplomat, Wazir discussed the incident: "While local officials admitted to me that it was an accident and we were not to blame, they nevertheless destroyed our livelihoods under the Frontier Crimes Regulation."

[16] Wazir ran for the seat of the National Assembly of Pakistan as an independent candidate from Constituency NA-41 (Tribal Area-VI) in the 2008 Pakistani general election but was unsuccessful.

[6] In 2018, he became one of the founding leaders of the Pashtun Tahafuz Movement (PTM) which emerged after the extrajudicial killing of Naqeebullah Mehsud at the hands of police in Karachi.

[23] He was offered a nomination on the Pakistan Tehreek-e-Insaf (PTI) ticket by Imran Khan to contest the 2018 general election from his Constituency NA-50 (Tribal Area-XI), which he declined.

The Taliban and al-Qaeda were running parallel courts and meting out punishments, but the government forces were largely relegated to military camps."

He also opposed the barbed barrier along the Durand Line and demanded that all historic routes on the Afghan-Pakistani border be ensured for trade and free movement of people.

[27][28][29] On 21 April 2018, a night before the PTM public gathering in Lahore, the police arrested Wazir along with several other leading activists, including Ismat Shahjahan and Fanoos Gujjar of the Awami Workers Party (AWP).

[30][31] The arrests were criticized by the public and notable politicians, including Maryam Nawaz, Pervaiz Rashid, and Bilawal Bhutto Zardari.

[32] On 30 November 2018, Wazir and Mohsin Dawar, his fellow parliamentarian and PTM leader, were traveling to Dubai, UAE to attend a Pashtun cultural event, but they were offloaded from their flight at Bacha Khan International Airport, Peshawar.

[40][41][42] Human rights activists and PTM members Alamzaib Mahsud and Qazi Tahir Maseed also appeared before the anti-terrorism court in Karachi at the same time, who had been similarly arrested for allegedly defaming state institutions.

[15][48] On 3 June 2018, when he was campaigning for the 2018 general election during the Islamic holy month of Ramadan, gunmen affiliated with the Taliban attacked Wazir and other supporters of the Pashtun Tahafuz Movement (PTM) in Wanna, South Waziristan.

[49] A local senior journalist, on condition of anonymity, told his sources confirmed that the attack was carried out by the Nazir Group, a faction of Taliban militants which operated in South Waziristan.

To condemn the act of the militant leader, Ali Wazir announced that a protest sit-in was to be held by PTM in Wanna from June 4.