Syed Hussein's academic career began at the Dewan Bahasa dan Pustaka publishing house, where he worked as head of the research department from 1958 onwards. He began lecturing part-time in philosophy at the University of Malaya in 1960 and served as the Head of the Cultural Division at the University's Department of Malay Studies from 1963 to 1967. He served as the Head of the Department of Malay Studies in the National University of Singapore from 1967 to 1988.