He was appointed Prefect of the Pontifical Household, the papal majordomo, by Pope Benedict XV on 16 June 1921.

Upon the death of Pope Benedict on 22 January 1922, Caccia-Dominioni and all other major Vatican officials, in accord with custom, automatically lost their positions during the sede vacante.

[3] Caccia-Dominioni was created Cardinal-Deacon of S. Maria in Domnica by Pope Pius XI in the consistory of 16 December 1935.

In virtue of his position of Protodeacon (the senior cardinal deacon), Caccia-Dominioni announced Pius XII's election and later crowned him on 12 March 1939.

[4] The OVRA had a file on him, which detailed that he often lured young boys to his apartment in Rome for sex, and that the pope had been aware of this.