In 1393 he fought with Andrea against the Ordelaffi of Forlì, but his occupation of Todi and Narni, then part of the neighbouring Papal States, attracted him the excommunication of Pope Boniface IX.
Hired by Gian Galeazzo Visconti together with his brother Andrea, he fought in the victorious battle of Casalecchio against Bologna, and was subsequently named governor of that city.
However, his territories in Lombardy were soon attacked by Francesco Bussone, condottiero of the new Visconti Duke Filippo Maria and provided with a strong army.
In 1424, in the course of the First War in Lombardy, the Florentine army led by the Malatesta brothers (with 10,000 cavalry and 3,000 infantry) was severely defeated at the battle of Zagonara.
He therefore lost Imola and Faenza to the Visconti, but managed to keep Fano thank to the intercession of Pope Martin V. In the following years Malatesta devote to humanistic studies and to embellish his city.