In 1481 he was Prior of the city, and later became a favourite of Piero di Lorenzo de' Medici, receiving from him, in 1493, the honour of being the Ambassador to the Kingdom of France.

He was elected gonfaloniere for life in 1502 by the Florentines, who wished to give greater stability to their republican institutions, which had been restored after the expulsion of Piero de' Medici and the execution of Savonarola.

Niccolò Machiavelli, author of The Prince and Discourses on Livy, served under him as second chancellor and as ambassador to Cesare Borgia, Rome and France.

He took refuge at Orašac (near Dubrovnik) in Dalmatia,[2] where he remained until the election of Pope Leo X, who summoned him to Rome and conferred many favours on him.

Soderini lived in Rome for the rest of his life and worked for the good of Florence, to which he was never allowed to return.