After finishing his law degree at the local university in 1616 he followed his family to Siena, where his father had been appointed governor of the city for Grand Duke Cosimo II.

In 1635 Malvezzi published Il ritratto del privato politico christiano, a biography of the Count-Duke of Olivares, valido or chief minister of King Philip IV of Spain.

Malvezzi's work soon appeared in a Spanish translation and attracted the attention of Olivares himself, who called him to Madrid, where he arrived in 1636, to serve as the official historian of the reign of Philip IV.

By the late 1630s Malvezzi's credentials as a scholar and historian were somewhat tarnished by the closeness of his relationship to Olivares; but his Romulus, published in his native Bologna in 1629, had won him an international reputation.

His taste for the paradoxical and the epigrammatic, for abrupt transitions and contrived obscurity was praised as “elegantly laconic”[13][14] and was much admired by Olivares who made him the historian of his regime.

He regarded Tacitus as the loftiest master of the “laconic style,” no less superior to the “asiatic than pure wine is to watered wine.” Its very obscurity imparts to the reader the same pleasure deriving from the metaphor inasmuch as it challenges him to integrate the apparent gaps in the sentence by intervening with his own wit.

[19] He composed a series of political biographies of famous princes from Roman and Jewish history probably reminiscent of Xenophon's Cyropaedia where it is easy to recognise Machiavelli's lasting influence: Romulo (1629), Tarquinio il Superbo (1632), and Davide perseguitato (1634).

[22] Henry Carey, 2nd Earl of Monmouth translated both Romulo and Il Tarquinio Superbo and had them published together in one volume in 1637, whereas the two Italian source texts had come out separately in 1629 and 1632.

John Nichols claimed that Thomas Gordon's commentaries on Tacitus were derivative from the work of Virgilio Malvezzi, Scipione Ammirato and Baltasar Alamos de Barrientos.