After the death of his father during the War of L'Aquila, he participated in Braccio da Montone's final defeat in that campaign; he fought subsequently for the Neapolitan army and then for Pope Martin V and the Duke of Milan, Filippo Maria Visconti.

In 1431, after fighting again for the Papal States, he led the Milanese army against Venice; the following year the duke's daughter, Bianca Maria, was betrothed to him.

The allegiance of mercenary leaders was dependent, of course, on pay; in 1433–1435, Sforza led the Milanese attack on the Papal States, but when he conquered Ancona, in Marche, he changed sides, obtaining the title of vicar of the city directly from Pope Eugene IV.

After some initial setbacks, he defeated the Neapolitan commander Niccolò Piccinino, who had invaded his possessions in Romagna and Marche, through the help of Sigismondo Pandolfo Malatesta (who had married his daughter Polissena) and the Venetians, and could return to Milan.

Sforza later found himself warring against Francesco Piccinino (whom he defeated at the Battle of Montolmo in 1444) and, later, the alliance of Visconti, Eugene IV, and Malatesta, who had allegedly murdered Polissena.

With the help of Venice, Sforza was again victorious and, in exchange for abandoning the Venetians, received the title of capitano generale (commander-in-chief) of the Duchy of Milan's armies.

[6] He also received the seigniory of other cities of the duchy, including Lodi, and started to carefully plan the conquest of the ephemeral republic, allying with William VIII of Montferrat and (again) Venice.

While the other Italian states gradually recognized Sforza as the legitimate Duke of Milan, he was never able to obtain official investiture from the Holy Roman Emperor.

He created an efficient system of taxation that generated enormous revenues for the government, his court became a centre of Renaissance learning and culture, and the people of Milan grew to love him.

In Milan, he founded the Ospedale Maggiore, restored the Palazzo ducale, and had the Naviglio d'Adda, a channel connecting with the River Adda, built.

After the peace, Sforza renounced part of the conquests in eastern Lombardy obtained by his condottieri Bartolomeo Colleoni, Ludovico Gonzaga, and Roberto Sanseverino d'Aragona after 1451.