He entered the Greek diplomatic corps in 1922 and served in several posts, rising to Permanent Vice Minister for Foreign Affairs in 1947–1948. In 1952 he was appointed permanent representative of Greece to NATO, and resigned from the diplomatic service the next year. He served as Minister for Trade in the 1961–1963 Konstantinos Karamanlis cabinet and, following Karamanlis' resignation and self-exile, Pipinelis served briefly as an interim Prime Minister of Greece from 17 June 1963 to 29 September 1963. On 20 November 1967 he was appointed as Minister of Foreign Affairs during the dictatorship. He held the post until his death of cancer on 19 July 1970 in Athens, aged 71.