He served as president of the Pontifical Commission for Vatican City State from 1939 and as Major Penitentiary from 1941 until his death, and was elevated to the cardinalate in 1935.

On 1 September 1903, Canali was made private secretary to Cardinal Rafael Merry del Val and entered the Roman Curia, in the Secretariat of State.

Canali was one of the cardinal electors in the 1939 papal conclave that selected Pope Pius XII, who appointed him the first President of the Pontifical Commission for Vatican City State on 20 March 1939.

Made Major Penitentiary on 15 October 1941, the Cardinal was appointed Pro-President of the Administration of the Patrimony of the Apostolic See in 1951 (remaining in that post until his death), and participated in the 1958 papal conclave, which resulted in the election of Pope John XXIII.

In virtue of his position as Cardinal Protodeacon, he both announced Pope John's election and later crowned him on 4 November 1958.

Not satisfied, Canali sought the support of the Vatican to remove the sovereign character of the Order of Malta and put it under the sole tutelage of the Holy See.