He later became professor of Greek (21 August 1868) and prefect of studies (19 November 1880) at the Pontifical Roman Seminary, and Substitute (or deputy) of the Secretariat of Apostolic Briefs on 1 June 1874.

Jacobini was raised to the rank of Domestic Prelate of His Holiness on 2 August 1877 and was named Secretary of the Sacred Congregation for Extraordinary Ecclesiastical Affairs on 19 September 1879.

He received his episcopal consecration on the following August 14 from Cardinal Edoardo Borromeo, with Archbishops Alessandro Sanminiatelli Zabarella and Francesco Folicaldi serving as co-consecrators, at the altar of the Chair of Saint Peter.

Pope Leo created him Cardinal Priest of Santi Marcellino e Pietro in the consistory of 22 June 1896 and he ceased to serve as Nuncio.

The Pope who received the news while giving audience to the Piedmontese pilgrims was deeply moved and returned hastily to his private apartments.