Majali was director of medical services for the Jordanian Armed Forces from 1960 to 1969. He also served as minister of health (1969–1971), minister of state for prime ministerial affairs (1970–1971 and 1976–1979) and also, minister of education (1976–1979). He was then named as president of the University of Jordan (1971–1976 and 1980–1989). In 1973, Majali was promoted to be a professor of medicine at the University of Jordan. He served as advisor to King Hussein starting in the late 1980s.
Majali was prime minister from May 1993 to January 1995, during which time he signed the 1994 Israel–Jordan peace treaty. When he was appointed prime minister, he was also given the portfolio of foreign minister. On 5 January 1995, he resigned from office. He again was prime minister from 1997 to 1998, after which he was appointed to the Jordanian senate.