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In his youth he was known for his modest lifestyle and stringent piety.
He studied at Perugia and Padua, was ordained a priest and swiftly appointed Bishop of Cremona, in 1560, in time to participate in the sessions of the Council of Trent from 1561 to 1563.
Pope Gregory XIII made him a Cardinal-Priest of Santa Cecilia in Trastevere on 12 December 1583.
Sfondrati was a close follower of Carlo Cardinal Borromeo, and when cardinal he celebrated the Requiem Mass for Borromeo on 7 November 1584.
Sfondrati was an intimate friend and a great admirer of Philip Neri, an Italian priest who died in 1595 and was canonised in 1622.

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