Cassiodorus was born at Scylletium, near Catanzaro in Calabria, Italy. His ancestry included some of the most prominent ministers of the state extending back several generations. His great-grandfather held a command in the defense of the coasts of southern Italy from Vandal sea-raiders in the middle of the fifth century; his grandfather appears in a Roman embassy to Attila the Hun, and his father served as Count of the sacred largesses and count of the private estates to Odovacer before transferring his allegiance to Theoderic. Under the latter, Cassiodorus' father (who bore the same name), rose to an even higher position, achieving the office of Praetorian Prefect, which held, under the Gothic kings, the same influence that it had previously in the court of Rome.
Cassiodorus began his career under the auspices of his father, about in his twentieth year, when the latter made him his consiliarius upon his own appointment to the Praetorian Prefecture. In the judicial capacity of the prefect, he held absolute right of appeal over any magistrate in the empire (or Gothic kingdom, later) and the consiliarius served as a sort of legal advisor in cases of greater complexity. Evidently, therefore, Cassiodorus had received some education in the law. During his working life he worked as quaestor sacri palatii c. 507–511, as a consul in 514, then as magister officiorum under Theoderic, and later under the regency for Theoderic's young successor, Athalaric. Cassiodorus kept copious records and letterbooks concerning public affairs. At the Gothic court his literary skill, which seems mannered and rhetorical to modern readers, was so esteemed that when in Ravenna he was often entrusted with drafting significant public documents. His culminating appointment was as praetorian prefect for Italy, effectively the prime ministership of the Ostrogothic civil government and a high honor to finish any career. Cassiodorus also collaborated with Pope Agapetus I in establishing a library of Greek and Latin texts which were intended to support a Christian school in Rome.
James O'Donnell notes:
[I]t is almost indisputable that he accepted advancement in 523 as the immediate successor of Boethius, who was then falling from grace after less than a year as magister officiorum, and who was sent to prison and later executed. In addition, Boethius' father-in-law (and step-father) Symmachus, by this time a distinguished elder statesman, followed Boethius to the block within a year. All this was a result of the worsening split between the ancient senatorial aristocracy centered in Rome and the adherents of Gothic rule at Ravenna. But to read Cassiodorus' Variae one would never suspect such goings-on.
There is no mention in Cassiodorus' selection of official correspondence of the death of Boethius.
Athalaric died in early 534, and the remainder of Cassiodorus' public career was dominated by the Byzantine reconquest and dynastic intrigue among the Ostrogoths. His last letters were drafted in the name of Vitiges. Around 537–38, he left Italy for Constantinople, from where his successor was appointed, where he remained for almost two decades, concentrating on religious questions. He notably met Junillus, the quaestor of Justinian I there. His Constantinopolitan journey contributed to the improvement of his religious knowledge.
Cassiodorus spent his career trying to bridge the 6th-century cultural divides: between East and West, Greek culture and Latin, Roman and Goth, and between an Orthodox people and their Arian rulers. He speaks fondly in his Institutiones of Dionysius Exiguus, the calculator of the Anno Domini era.
In his retirement, he founded the monastery of Vivarium on his family estates on the shores of the Ionian Sea, and his writings turned to religion.