Borso d’Este served as advisor to his older brother Leonello, Marquis of Ferrara and Lord of Modena, Reggio, Polesine and Garfagnana. Because Leonello's son, Niccolò, was still a minor upon his father’s death on 1 October 1450, Borso became ruler of Ferrara. He was the last Marquis of Ferrara and the first Duke of Modena and Reggio (as of 1452), appointed by Emperor Frederick III of Habsburg. Frederick III then appointed him Count of Rovigo the following year, and, in 1471, he was appointed Duke of Ferrara by Pope Paul II. He passed away just a few months afterwards.

Lasting about two decades, his rule was characterised by stability, peace and prosperity. This was in part thanks to his diplomatic skill and astuteness, which allowed him to implement fruitful policies, though often seen as backhanded and unscrupulous. His rule was marked by the exaltation of himself as the ideal prince, corresponding in fact to positive, fruitful results for Ferrara and its surroundings.

His main achievements include the establishment of the Consiglio di Giustizia (Council of Justice, 1453), the reclamation of the Polesine wetlands, and the expansion of the city to the south-east, known as the Addizione Borsiana (Borsian Addition).

He wasn’t as educated or cultured as Leonello d’Este, but he protected the arts and the university. He can be credited with commissioning the frescoes in the Salone dei Mesi in Palazzo Schifanoia and numerous projects to restore and amplify buildings, such as Palazzo Schifanoia itself, Palazzo Paradiso, the Delizia di Belfiore and the Delizia of Belriguardo. Though literature didn’t have the same momentum during Borso’s rule as it did under his predecessor, architecture flourished. Borso himself oversaw the work done at La Certosa, at the time located outside the city walls to the north-west.

His commissions include the famous Borso d’Este Bible, the most notable illuminated manuscript in Italy, completed between 1455 and 1461. It was entrusted to a team of artists, led by illuminators Taddeo Crivelli and Franco Dè Russi, who worked hard to create the masterpiece: 600 pages of parchment, illuminated on both sides.

«Vedi Leonello, e vedi il primo duce,
Fama de la sua età, l’inclito Borso,
Che siede in pace, e più trionfo adduce
Di quanti in altrui terre abbino corso.
Chiuderà Marte ove non veggia luce,
E stringerà al Furor le mani al dorso.

Di questo signor splendido ogni intento
sarà che il popul suo viva contento»

(L. Ariosto, Orlando Furioso, III, 45)