Nathan began his career in the Singapore Civil Service as a medical social worker in 1955 and was appointed seamen’s welfare officer in 1956. 

In 1962, he was seconded to the Labour Research Unit of the Labour Movement, first as assistant director and later as director, until January 1966. He continued as a member of its board of trustees till April 1988.

In February 1966, Nathan was transferred to the foreign ministry where he served as assistant secretary and rose to be deputy secretary before being appointed acting permanent secretary of city state's home ministry in January 1971. 

In August of the same year, Nathan moved to the defence ministry where he served as a director with the rank of permanent secretary.

In February 1979, he returned to the foreign ministry and became its first permanent secretary till February 1982. 

Thereafter, he became the executive chairman of the Straits Times Press media group. He was in the directorship of several other companies in the period between 1982 and 1988.