He was born in Florence, Italy, the son of Michele Accolti, patrician of Arezzo, and Lucrezia Alamanni.

Accolti began his ecclesiastical career in the Roman Curia, following the steps of his uncle.

He was promoted bishop of Cadiz on 24 July 1521, before reaching the canonical age of 27, so he was named administrator after his uncle.

Then he was transferred to Cremona on 16 March 1523 again after his uncle and then named Secretary of Pope Clement VII the same year.

The new Pope Paul III deprived him of his cardinalate on 27 August 1534, and imprisoned him in the Castel Sant'Angelo, accusing him of misspending 19,000 ducats for the expedition against the Turks.