Mufti Mehmood was born on January 1919 in Paniala, District Dera Ismail Khan (N.W.F.P.). He acquired his religious education from Jamia Qasimiya in Muradabad. During 1937 elections was a campaigner of Jamiat-ul-Ulama-e-Hind. After completion of his education in 1941 he served as a teacher in Isa Khel Mian Wali till 1944. During the ‘Quit India’ movement in 1942 against the British, Mufti Mahmood took part in the campaign on behalf of Jamiat-ul-Ulema-e-Hind. He was not only an elected Member of its Majlis-e-Amila but also Councilor the party. In 1950, he got a teaching job in Madrassa Qasim-ul-Uloom in Multan. Later on, he served at positions of chief Mudarras, In charge of Education, Chief Mufti, Sheikh-ul-Hadith, and Muhtamim. As a Mufti, he passed on at least 25,000 Fatawa.
Mufti Mahmood took an active part in Tahreek-e-Khatm-e-Nabuwwat in 1953. Being deadly against Ayub Khan’s One Unit Scheme, he was arrested in 1956. In April 1962, he took part in the elections for the National Assembly Seat for the first time under Basic Democracy Program and defeated all the opponents. On 14th July 1962 when law was passed to re-instate all the Political Parties, Mufti Mahmood took charge of Jamiat-Ulema-Islam as Qaim Maqam Ameer and in 1963 he became its Naib Ameer. He was critical of family planning and other policies of Ayub Khan government. Mufti Mahmood was one of the central leaders of “Jamhoori Majlis-e-Amal” that was formed in Dacca by Pakistan’s political parties in Dacca on 8 January 1968. Then in May 1970, Pakistan’s 18 religious and political Parties formed a “Muttahida Deeni Mahaz” whose President was Mufti Mahmood. In December, Elections were held and Mufti Mahmood gained a landslide victory against Zulfiqar Ali Bhutto in the Dera Ismail Khan constituency.
On 26 March, the three main political parties made an agreement that was signed by Z. A. Bhutto from PPP,