Sindh Madressatul Islam was established by a great educationist and visionary of his times, Khan Bahadur Hassanally Effendi (1830-1895). The institution was declared open on 1st September 1885 and the foundation stone of its Main Building was laid by the Viceroy of India, Lord Dufferin, on 14th November 1887.
The greatest distinction of Sindh Madressah has been that founder of Pakistan, Quaid-i-Azam Mohammad Ali Jinnah studied here for the longest spell of his academic life from 1887 to 1892 and revered his alma-mater to the extent that he bequeathed one-third of his personal property to Sindh Madressah through his last will. The institution also produced some of leading luminaries of Pakistan including Sir Shahnawaz Bhutto, Sir Ghulam Hussain Hidayatullah, Haji Sir Abdullah Haroon, Dr. Umer Bin Mohammad Daudpota and Allama I.I. Kazi in addition to spreading the light of education far and wide.
After serving the people of this region for about 58 years as a school, Sindh Madressah was upgraded to "Sindh Madressah College" by its distinguished alumnus Quaid-e-Azam Mohammad Ali Jinnah on 21st June 1943. With passage of time the institution expanded, and one after the other, the following institutions were founded; SM Science College, SM Arts and Commerce College, SM Law College, Fatima Jinnah Girls College and a host of other schools. Another great leader of Pakistan, Shaheed Zulfikar Ali Bhutto, remained on the faculty of SM Law College.
There had been a dream of elevating Sindh Madressatul Islam to University since its establishment in 1885. The oldest proponent of this idea was Sir Syed Ahmed Khan, who advised Hassanally Effendi in these words: "Don't think of a school only, aim at a college to expand into a university." Finally, after about a century and a quarter since its establishment at the hands of Khan Bahadur Hassanally Effendi and 69 years after attaining the status of a college at hands of Quaid-e-Azam, Sindh Madressatul Islam was elevated to the level of a University under the directives of President Asif Ali Zardari on 21st February 2012.
Sindh Assembly passed the Sindh Madressatul Islam University Act on December 22, 2011 giving standing ovation to the institution and its founder for services rendered. After Assenting to the Bill, Governor Sindh Dr. Ishrat ul Ebad Khan handed over the charter of Sindh Madressatul Islam University and letter of his appointment as its first Vice Chancellor to Dr. Muhammad Ali Shaikh.