He was born at Brescia, the son of Pandolfo III Malatesta and Antonia da Barignano.
Two years later, he suppressed several riots in the city spurred by the Malatesta of Pesaro; the people turned against the leader, and hailed him and his brother Sigismondo Pandolfo as lords.
At the time his lands included Cesena, Bertinoro, Meldola, Sarsina, Roncofreddo and the Piviero di Sestino.
In 1434, when he was 16, he married Violante da Montefeltro (daughter of Guidantonio count of Urbino) then four.
Aside from his military deeds, Malatesta Novello is celebrated for his large building programs in Cesena, such as the Convent di S. Maria (1438), the strengthening of the Rocca Malatestiana and enlargement of the city walls (1441); in 1452 he founded the Biblioteca Malatestiana, the first public library in Europe.