He was born and died in Florence, Italy, and was one of the chief figures in the company of learned men which gathered around the patronage of Cosimo de' Medici.
Niccoli's chief services to classical literature consisted in his work as a copyist and collator of ancient manuscripts; he corrected the text, introduced divisions into chapters, and made tables of contents.
The pursuit of ancient manuscripts was a dangerous and expensive task; agents working in the field at the time included Poggio Bracciolini.
He regarded himself as an infallible critic, and could not bear the slightest contradiction; his quarrels with Francesco Filelfo, Guarino da Verona and especially with Traversari created a great sensation in the learned world at the time.
He was extremely indebted prior to his death, after which Cosimo offered to cover all of his outstanding payments to debtors in exchange for control over his collection of 800 manuscripts valued at around 6,000 florins.