Cicognani continued his studies at the Pontifical Roman Athenaeum S. Apollinare, and in 1910 he was appointed an official of the Sacred Congregation for the Discipline of the Sacraments.

First raised to the rank of monsignor in 1917, he taught at his alma mater of the Athenaeum S. Apollinare from 1921 to 1932, and then entered the Roman Curia, as substitute adjunct of the Consistorial, on 16 December 1922.

After holding a variety of pastoral and curial positions, Cicognani was appointed Apostolic Delegate to the United States and Titular Archbishop of Laodicea in Phrygia on 17 March 1933.

He received his episcopal consecration on the following 23 April from Cardinal Raffaele Rossi, with Archbishops Giuseppe Pizzardo and Carlo Salotti serving as co-consecrators, in the Roman church of Santa Susanna.

Cicognani would remain Apostolic Delegate to the United States, serving as liaison between the American hierarchy and the Vatican, for the next 25 years.

In a letter dated 22 June 1943 to American representative Myron C. Taylor, he said: "It is true that at one time Palestine was inhabited by the Hebrew Race, but there is no axiom in history to substantiate the necessity of a people returning to a country they left nineteen centuries before ...