Husain responded to the nationalist leader Mahatma Gandhi's (Gandhi, Mohandas Karamchand) appeal to Indian youth to shun state-supported institutions; he helped found the Muslim National University in Aligarh (later moved to New Delhi) and served as its vice-chancellor from 1926 to 1948. At Gandhi's invitation, he also became chairman of the National Committee on Basic Education, established in 1937 to design a Gandhian syllabus for schools.

In 1948 Husain became vice-chancellor of Aligarh Muslim University, and four years later he entered the upper house of the national Parliament. In 1956–58 he served on the executive board of the United Nations Educational, Scientific, and Cultural Organization ( UNESCO). He was appointed governor of Bihar state in 1957 and was elected vice president of India in 1962. As the official Congress Party candidate, he was elected president of India in 1967 and served until his death.