Born in Florence, he was appointed to numerous important positions in that city. He was ambassador in Milan and a protagonist of the Peace of Lodi in 1454.
The first advisor of Cosimo de' Medici the Elder, he helped in him to return in Florence from his exile. Cosimo recommended that Florence was governed under Neroni's directive after his death, but the ineptitude and the tyrannic behaviour showed by Cosimo's son, Piero the Gouty, pushed Neroni to take part in the 1466 conjure against him led by Luca Pitti, Angelo Acciaiuoli and Niccolò Soderini. Piero, however, was warned of the plot and crushed all its participants. Neroni and his sons were declared as "rebel", all their assets confiscated.