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Cardinalate

After his uncle was elected Pope Sixtus IV on 10 August 1471, Giuliano was appointed Bishop of Carpentras in the Comtat Venaissin on 16 October 1471. In an act of overt nepotism he was immediately raised to the cardinalate on 16 December 1471, and assigned the same titular church as that formerly held by his uncle, San Pietro in Vincoli. Guilty of serial simony and pluralism, he held several powerful offices at once: in addition to the archbishopric of Avignon he held no fewer than eight bishoprics, including Lausanne from 1472, and Coutances (1476–1477).

In 1474, Giuliano led an army to Todi, Spoleto, and Città di Castello as papal legate. He returned to Rome in May in the company of Duke Federigo of Urbino, who promised his daughter in marriage to Giuliano's brother Giovanni, who was subsequently named Lord of Senigallia and of Mondovì. On 22 December 1475, Pope Sixtus IV created the new Archdiocese of Avignon, assigning to it as suffragan dioceses the Sees of Vaison, Cavaillon, and Carpentras. He appointed Giuliano as the first archbishop. Giuliano held the archdiocese until his later election to the papacy. In 1476 the office of Legate was added, and he left Rome for France in February. On 22 August 1476 he founded the Collegium de Ruvere in Avignon. He returned to Rome on 4 October 1476.

In 1479, Cardinal Giuliano served his one-year term as Chamberlain of the College of Cardinals. In this office he was responsible for collecting all the revenues owed to the cardinals as a group (from ad limina visits, for example) and for the proper disbursements of appropriate shares to cardinals who were in service in the Roman Curia.

Giuliano was again named Papal Legate to France on 28 April 1480, and left Rome on 9 June. As Legate, his mission was threefold: to make peace between King Louis XI and the Archduke Maximilian of Austria; to raise funds for a war against the Ottoman Turks; and to negotiate the release of Cardinal Jean Balue and Bishop Guillaume d'Harancourt (who by then had been imprisoned by Louis for eleven years on charges of treason). He reached Paris in September, and finally, on 20 December 1480, Louis gave orders that Balue be handed over to the Archpriest of Loudun, who had been commissioned by the Legate to receive him in the name of the Pope. He returned to Rome on 3 February 1482. Shortly thereafter the sum of 300,000 ecus of gold was received from the French in a subsidy of the war.

On 31 January 1483 Cardinal della Rovere was promoted suburbicarian Bishop of Ostia, in succession to Cardinal Guillaume d'Estouteville who had died on 22 January. It was the privilege of the Bishop of Ostia to consecrate an elected pope a bishop, if he were not already a bishop. This actually occurred in the case of Pius III (Francesco Todeschini-Piccolomini), who was ordained a priest on 30 September 1503 and consecrated a bishop on 1 October 1503 by Cardinal Giuliano della Rovere.

Around this time, in 1483, an illegitimate daughter was born, Felice della Rovere.

On 3 November 1483, Cardinal della Rovere was named Bishop of Bologna and Papal Legate, succeeding Cardinal Francesco Gonzaga, who had died on 21 October. He held the diocese until 1502. On 28 December 1484, Giuliano participated in the investiture of his brother Giovanni as Captain-General of the Papal Armies by Pope Innocent VIII.

By 1484 Giuliano was living in the new palazzo which he had constructed next to the Basilica of the Twelve Apostles, which he had also restored. Pope Sixtus IV paid a formal visit to the newly restored building on 1 May 1482, and it may be that Giuliano was already in residence then.