Early career and Pazzi ConspiracyBorn in poverty in Savona, Riario was the son of Antonio Sansoni and Violante Riario, a niece of Francesco della Rovere, who became in 1471. Being the relative of a , he was created Cardinal of San Giorgio in Velabro on 10 December 1477 and was named Administrator of several s: ( diocese of Cuenca, diocese of Pisa, diocese of Salamanca, diocese of Treguier, diocese of Osma). These gave him a handsome income, and no obligations except to appoint a vicar. He was then only sixteen years old and a student of canon law at the University of Pisa. While returning to Rome in the spring of 1478, Riario halted in Florence, where he became a witness to the Pazzi Conspiracy against the Medici. Despite his innocence, Rafaelle was arrested by the Florentine authorities because he was a relation of the conspirators Girolamo Riario, his mother's brother and the head of the plot, and the Archbishop Francesco Salviati (archbishop), Francesco Salviati. His release a few weeks later was arranged by Lorenzo de' Medici. On 22 June 1478 he was received formally as a cardinal by the Pope in Siena and four days later he was sent as legate to Perugia. It was not until 1480 that Raffaele was ordained priest and received the entitlement of San Lorenzo in Damaso.
Riario in the Papal CourtIn 1484, Riario was engaged in the war which broke out between the Orsini family, Orsini and the Colonna family, trying to secure in vain the life of his friend Lorenzo Oddone Colonna, who was charged of having murdered an Orsini and was executed by Sixtus IV. In 1488, Pope Innocent VIII sent Cardinal Riario as a legate to his maternal uncle Girolamo Riario, at the time governor of Forlì and Imola, who was revolting against the Holy See. Meanwhile, the Cardinal had already commissioned the erection of his palace beside the church of San Lorenzo in Damaso (1486). It is said that Franceschetto Cybo, the infamous son of Innocent VIII, lost in one single night 15,000 ducats at a card game which took place in Raffaele's residence. When the Pope asked the Cardinal to return his son's money, the latter answered that he was sorry, but he had already used it to finance the construction of his palace. As cardinal Camerlengo of the Holy Roman Church, Camerlengo, Riario is usually praised for ensuring order in after the death of Innocent VIII. He was a candidate for the papal tiara in the Papal conclave, 1492, Conclave of 1492 but excluded from the first ballots due to his young age. He finally voted for Rodrigo Borgia (Pope Alexander VI), receiving the lucrative Bishopric of Cartagena as a reward for his support. During Alexander VI’s reign (1492–1503), Riario gained distinction as diplomat and councillor of the papal throne. In 1493, he was sent as legate to Caterina Sforza, Girolamo Riario's widow, to prevent her from allowing the French troops to pass through Forlì and Imola. Pope Julius II (1503–1513), Riario's relative but not always his ally, raised him to the Bishop of Ostia, Bishopric of Ostia e Veletri, the first hierarchical see in the Papal States.
Engagement in the plot against Leo X and deathIn June 1517, Alfonso Petrucci, Cardinal Petrucci and others conspired against Pope Leo X (Giovanni dei Medici). Cardinal Riario refused to participate in the plot but was at least aware of Petrucci's intentions to murder the Pope and did nothing to prevent it. Leo was notified about the plot, arrested the conspirators and ordered their execution. Riario, whose entanglement in the Pazzi conspiracy had not been forgotten by the Medici Pope, secured his head only by surrendering his palace beside San Lorenzo in Damaso to the Pope. Leo transferred it to his cousin Clement VII, Giulio de' Medici, Vice-Chancellor of the Holy See, who rendered it the seat of the Apostolic Chancery. Thus the Palazzo Riario is henceforward known as . Riario died in Naples, at the age of sixty. His tomb is located in the church of Basilica dei Santi Apostoli in Rome.
Art patronage and reputationA lover of fine arts and especially sculpture, Cardinal Riario's artistic choices foreshadow the arrival of High Renaissance in . His gigantic residence, influenced by the Florentine architecture, is the first building of the new monumental style which prevailed in the Holy City under Julius II. Riario is also credited for noticing the talent of the young Michelangelo. In 1496, Cupid (Michelangelo), the Sleeping Cupid was treacherously sold to him as an ancient piece: the aesthetic prelate discovered the cheat, but was so impressed by the quality of the sculpture that he invited the artist to Rome, where Michelangelo worked on the three major commissions of his career. Raffaele Riario is generally considered a prelate typical of his era: indifferent in religious matters, rather a statesman than a priest, rather a Maecenas than a theologian.
In popular cultureRaffaele Riario appears in seasons 2 and 3 of the 2016 ''Medici (TV series), Medici'' tv series. He is played by Francesco di Raimondo in season 2 and Loris De Luna in season 3.