At the age of twenty-five he held several rich livings, had been notary and protonotary to the Curia and was first secretary to the pope, in which capacity he conducted the correspondence with the nuncios (among them Pier Paolo Vergerio in Germany) and a host of other duties.
By his conduct at the conference with Francis I of France at Marseille he won the favour of Catherine de' Medici and other influential personages at the French court, who in later days befriended him.
He became a leading spirit in the literary and religious circle that gathered round Valdés in Naples, and that aimed at effecting from within the spiritual reformation of the church.
Carnesecchi was in Venice when the news reached him, and betook himself to Florence, where, thinking himself safe, he was betrayed by Duke Cosimo I de' Medici, who wished to curry favour with the pope.
On 21 September 1567 a sentence of degradation and death was passed on him and sixteen others, ambassadors from Florence vainly kneeling to the pope for some mitigation, and on 1 October he was publicly beheaded and then burned.