While a student, he began writing for leftist publications, mostly about international relations.[2] He was the leader of the Bucharest Communist students' organization until 1940.[2]
In 1944 he was working at the Central Statistics Bureau, and in 1948 he was appointed as one of the vice ministers of the Ministry of National Defence, with the rank of lieutenant colonel.[2] Promoted shortly after to colonel, he served from 1950 to 1952 as head of the National Military Circle.[3] In 1959 he was named chief of the Higher Political Division of the Army, with the rank of major general.[2] Between 1955 and 1960 he was vice president of the State Planning Committee.[2]
In 1960, Mănescu became Director of the Political Division in the Ministry of Foreign Affairs. From 1960 to 1961, he served as Ambassador to Hungary. He was appointed Minister of Foreign Affairs in March 1961, a post in which he remained until 1972. Other important posts he held were that of vice president of the United Socialist Front, president of the Romanian Group of the Inter-Parliamentary Union, ambassador to France (1977–1982).[2]
Mănescu, who became a member of Romanian Communist Party's Central Committee in 1965,[2] was the first communist elected president of the UN General Assembly.[4]