He served in Bangladesh's first post-independence government from 1972 to 1975, initially as law minister and chairman of the drafting committee in the Constituent Assembly. Hossain led the process which produced the 1972 Constitution of Bangladesh. He then served as foreign minister, and led Bangladesh to join the United Nations in 1974. As energy minister, Hossain later enacted the Bangladesh Petroleum Act. He was a research fellow and visiting fellow at Oxford University during the late 1970s. In 1981, he ran as an opposition candidate for president against Abdus Sattar. Hossain fell out with Awami League president Sheikh Hasina during the 1990s, and formed the Gono Forum (People's Forum) party. Hossain has often worked with the United Nations and the Commonwealth of Nations. He was also considered as a candidate for the post of UN Secretary General.