He previously served as Secretary of the Congregation for Bishops after more than twenty years in the diplomatic service of the Holy See that included stints as Apostolic Nuncio to Haiti, Paraguay, India, Nepal, and Brazil.

On 15 January 1992, Pope John Paul II appointed him Titular Archbishop of Diocletiana and Apostolic Nuncio to Haiti.

At the end of that conclave, Pope Francis gave Baldisseri his red zucchetto, indicating that he would soon make him a cardinal.

[13] In early September 2013, Baldisseri was part of a group of 30 officials of the Roman Curia who met with Pope Francis to offer their views and concerns with respect to his proposed reorganization of the Vatican's administrative apparatus.

[18] Baldisseri asked the episcopal conferences to distribute the poll "immediately as widely as possible to deaneries and parishes so that input from local sources can be received."

[22][23] The topics raised in the questionnaire included contraception, divorce and remarriage, same-sex marriage, premarital sex and in vitro fertilization.

We need to present the beauty of the family to the world" and "we want to walk and view the global challenges to find an answer in the light of the Gospel".

[25] Pope Francis raised Baldisseri to the rank of Cardinal-Deacon on 22 February 2014 and assigned him to the deaconry of Sant’Anselmo all'Aventino.

[28] Pope Francis appointed Mario Grech Pro-Secretary General of the Synod of Bishops on 2 October 2019 to serve in anticipation of Baldisseri's retirement.