Giuseppe Paupini was born in Mondavio, Italy. He was educated at the local seminary of the diocese of Fano and later at the Pontifical Regional Seminary "Pio XI" and at the Pontifical Lateran University where he earned a doctorate in canon law. He was ordained on 19 March 1930 in Fano. He worked in the diocese of Fano and as a faculty member of its seminary from 1932 until 1939. He entered the diplomatic service of the Holy See in 1939 as attaché of the nunciature to France and later as secretary of the nunciature to Italy. He was chargé d'affaires of the nunciatures in Honduras, Nicaragua and Cuba between 1947 and 1951. He was promoted to counselor of nunciature in 1951. Between 1952 and 1956 he fulfilled pastoral assignments in the Diocese of Rome.