In 1375 Coluccio was appointed Chancellor of Florence, the most important position in the bureaucracy of the Florentine Republic. The most important achievement of his time in office was saving Florence from the ambitions of Giangaleazzo Visconti of Milan. Despite being severely outclassed by the Milanese forces, the Florentines succeeded in holding on to their independence over twelve years of war. Coluccio played an important part in rallying the Florentine people to defend their tradtional liberty and republicanism. The war ended upon the death of Giangaleazzo in 1402, leaving Florence in a powerful position in northern Italy.
Coluccio's cultural achievements are perhaps even greater than his political ones. A skilled writer and orator, Collucio drew heavily upon the classical tradition. He spent much of his salary on amassing a collection of 800 books, a large library by the standards of the time. He also pursued classical manuscripts, making a number of important discoveries, the most important being the lost letters of Cicero, which overturned the entire medieval conception of the Roman statesman. Coluccio also did imprtant studies of history, tying Florence's origin not to the Roman Empire but to the Roman Republic. In his lifetime, the study of secular literature, especially pagan literature, was strongly frowned upon by the Roman Catholic Church. Coluccio played an important part in changing these viewpoints, frequently engaging in theological debates on the merits of pagan literature with Church officials.