Born in Ferrara on 9 November 1383, Niccolo was the son of Alberto d'Este and Isotta Albaresani.

As a minor he was guided by a Regency Council supported by the Republics of Venice, Florence and Bologna.

In 1403 he joined the league formed against Gian Maria Visconti, Duke of Milan, being appointed Captain General of the Papal Army by Pope Boniface IX.

Two years later, fearing the ambitions of Filippo Maria Visconti, he ceded to him the possession of Parma.

The role of Niccolò as a prestigious leader in Italy was confirmed when his city was chosen as the seat of a council in 1438.