Muhammad Yusuf was born in 1952 into a religious family in Uzbekistan's Andijon Province. He received his education at Tashkent's Islamic Institute in 1971-75 and continued his studies in Libya. From 1982-89 he served as deputy director, and later director, of the Al-Bukhari Islamic Institute in Uzbekistan. In 1989, he became the head of the Religious Administration of Muslims in Central Asia and Kazakhstan. When Uzbekistan gained its independence in 1991, he became the country's chief mufti, its highest spiritual authority.

Muhammad Yusuf was a popular and respected religious leader, but in 1993 he was forced to leave Uzbekistan under pressure from the country's authorities, who were apparently preparing to charge him with aiding the Islamic opposition in neighboring Tajikistan's civil war. When religious extremism emerged as an increasingly pressing issue in Uzbekistan in the late 1990s, Muhammad Yusuf criticized Uzbek authorities' efforts to fight the phenomenon with police methods. Nevertheless, the Uzbek government officially invited the former chief mufti to return to his homeland in 1999.

In 2003, the Uzbek government finally allowed Muhammad Yusuf to publish two books on Islam. A consistent proponent of fighting extremism through education, Muhammad Yusuf set up an educational website (http://www.islam.uz) in September 2004 with extensive information in Uzbek and Russian about Islamic beliefs and practices. He is the author of numerous works of Islamic scholarship, including a multivolume collection of utterances by the Prophet Muhammad and a commentary on the Koran.