One of the powerful d'Este family of Ferrara she was very well educated in her youth and exposed to many of the new renaissance ideas. At the age of 16 she was married to Francesco Gonzaga, Marquis of Mantua. Under her auspices this court became one of the most cultured in Europe. Many important artists, writers and thinkers being drawn to it.
After the death of her husband Isabella ruled Mantua as regent for her child. She began to play an important role in Italian politics, steadily advancing Mantua's position. Her many important accomplishments include advancing Mantua to a Duchy and obtaining a cardinalate for her younger son.