He married Elisabetta da Varano, who gave him seven children : Galeazzo, Carlo, Galeotto, Paola, Pandolfo, Cleofa and Taddea.
In 1390 he fought against the Bolognesi led by Giovanni da Barbiano and later was hired by Republic of Florence against the Visconti of Milan.
In 1394 he served antipope Benedict XIII, who named him captain general of Bologna, to fight against pope Boniface VIII.
The conflict lasted until 1412: Malatesta again made peace with the pope, and thenceforth warred against antipope John XXIII.
As a patron of the arts, he had housed in Persaro figures such as Francesco Casini and the painter Mariotto di Nardo, and was in correspondence with humanists Coluccio Salutati and his daughter-in-law, Battista Malatesta.