When the Guelphs who supported the Pope against the Ghibellines of the Empire were expelled from Genoa, it is then that the fortress of Monaco was taken overnight on January 8, 1297 with François Grimaldi disguising himself off as a Franciscan friar.

When the Great Western Schism broke out, Rainier first remained in the obedience of Urban VI, elected in Rome; but it was not long before he joined the Pope of Avignon, Clement VII, in 1378.

During his reign, a papal bull dated February 19, 1524 from Pope Clement VII expressly consecrated the autonomy of Monaco with "its Lord not recognizing any superior from the temporal point of view.

[7] Innocent XII was finally favorable to the rights of the House of Bourbon, and allowed Philip, Duke of Anjou to take over the throne of Spain, thus causing a diplomatic victory for Louis Grimaldi.

On February 12, 1802, the ship carrying the remains of Pope Pius VI who died in Valence as a prisoner of the French Directory, was forced by a storm to make a stopover in Monaco.

But on January 11, 1814, it was a living Pope Pius VII returning from his captivity at Fontainebleau who passed through La Turbie and gave the locals of Monaco the opportunity to come cheer him in crowds along the road.

On September 28, 1887, a sovereign ordinance made state law the provisions of the said bull, which recalls the Concordat of Bologna through the role given to the Prince in the appointment of bishops.

On July 25, 1981, in Vatican City, an agreement was signed between the Holy See and the Principality of Monaco, Conventio inter apostolicam sedem et principatum monoecum[11] which can be considered as a concordat between these two countries.

This new provision was taken with a view to conforming the bull Quemadmodum sollicitus to the orientations given by the Second Vatican Council: it was a question of adjusting an incongruity of canon law while preserving the specificity of the relationship between the Holy See and Monaco due to their history and their status as microstates.

[13] In exchange, on July 30, 1981, through the papal bull entitled Apostolica haec, Pope John Paul II raised the episcopal see of Monaco to the dignity of archiepiscopal see.

In 2005, accompanied by his chief of staff Jean-Luc Allavena and the chaplain of the palace, Canon César Penzo, Prince Albert went to Rome to discuss the potential strengthening of links between Monaco and the Holy See, and offered to the sovereign pontiff a bronze statue of Sainte Dévote, created by Cyril de La Patellière.

On September 26, 2006, Prince Albert II received at the Palace the letters of credence of Monsignor André Dupuy, Extraordinary Apostolic Nuncio and Plenipotentiary of the Holy See.

On January 12, 2013, Prince Albert II presented his new wife Charlene, dressed in the tradition of the privilège du blanc, to Pope Benedict XVI during a private audience at the Vatican.