Born in Rome, the son of Agabito Cesarini, he became close to the Medici family, particularly Cardinal Giovanni di Lorenzo de' Medici, the future Pope Leo X. He was made cardinal deacon on July 1, 1517 and received the deaconry of Sts. Sergius and Bacchus, opting for the deaconry of Santa Maria in Via Lata in 1523. He became known for his patronage of writers and artists.
He served as apostolic administrator of Pamplona, Spain from 1520 to 1538; that of Alessano, Italy from 1526 to 1531; that of Otranto, Italy from 1526 to 1536; that of Gerace, Italy from 1536 to 1538; that of Catanzaro, Italy briefly in 1536; that of Oppido Mamertina, Italy from 1536 to 1538 (resigning in favor of his natural son, Ascanio Cesarini, who succeeded him in that see from 1538 to 1542); and that of Cuenca, Spain from 1538 to his death.
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- Marino Sanudo, Patricia H. Labalme and Laura Sanguineti White, Venice, Cità Excelentissima, (John sHopkins University Press, 2008), 184.
- Salvador Miranda, “The Cardinals of the Holy Roman Church, Biographical Dictionary, Pope Leo X (1513-1521), Consistory of July 1, 1517” (with bibliography) 
- “Alessandro Cardinal Cesarini (Sr.),” catholic-hierarchy.org