The rule of Milan by the Sforza family began with Francesco Sforza (1401-1466), who replaced the Visconti family.

The Duke of Milan, Filippo Maria Visconti had called Francesco to his service in 1425, but only in 1431 did he have the chance of employing him permanently. He promised him the hand of his daughter Bianca Maria, whom he married in 1441.

After the death of Filippo Maria Visconti in 1447, the Milanese formed a communal government and created the so-called Repubblica Ambrosiana (1447-1450), that soon suffered from external pressure, especially from the Venetian Republic.

Francesco, called to protect the Milanese against Venezia, succeeded twice, against the Venetian armies and against the reason of public rulers.

After a siege, he finally took Milan in 1450. The people then gave him the title of duke which could be passed on to his descendants.

As Duke of Milan, Francesco Sforza promoted order and economic growth, and, after the Peace of Lodi in 1454 (that settled the controversy raised by the acquisition of the title of duke), Italian Governments acted in order to preserve peace and stability, thanks to the diplomatic efforts of the Sforza and the Medici of Florence.

Then, in 1464, Duke Francesco conquered the city and the State of Genoa, thus becoming the absolute ruler of most of present Northern Italy.

He governed the Duchy of Milan, of Parma and Piacenza, the State of Genoa and Corsica.

As Duke of Milan, Francesco took appropriate measures in order to overcome the economic difficulties that weighed on the people after many years of war.

With economic growth, the construction of such buildings as the Ospedale Maggiore (by Filarete in 1457) and the new Castello Sforzesco (that had been almost destroyed under the Repubblica Ambrosiana) begun.

Francesco also had the figure of a patron, and called philosophers and literary men to his side.

Many of them, such as Filelfo, composed and dedicated their works to him.

He is also responsible for the introduction of the art of printing in Milan and Lombardy, which would be afterwards supported by his successors.

With his wife Bianca Maria he had many children, among them Galeazzo Maria, Duke of Milan, Ludovico the Moor and Ippolita, who married Alfonso II, the future king of Naples.

Among his natural children, it is worth mentioning Sforza, the first Count of Borgonovo, and Polissena, who became the wife of Sigismondo Pandolfo Malatesta, Lord of Rimini.
  In 1466, Galeazzo Maria Sforza (1444 1476) succeeded his father Francesco to power in Milan, but ten years later he was deprived of power by a group of conspirators from his own court, which afterwards had him executed.

His heir, young Giovanni Galeazzo Maria Sforza (1468 1493) actually gave his Galeazzo Maria Sforza’s brother Ludovico "the Moor" (1451 1510) the occasion he was waiting for to lay his hands on the title of duke.

He finally succeeded in 1494, when Emperor Maximilian invested him as the Duke of Milan, an act that also implied the emperor's supreme control.

Ludovico's claims, including the kingdom of Naples in the person of Isabella d'Aragona, wife of Duke Giovanni Galeazzo, were cause of instability in many parts of Italy, as well as the intervention of Charles VIII, King of France. Ludovico himself had called Charles VIII to take part in the conquest of the kingdom of Naples. The French King Charles VIII, and then Louis XII, would later become Ludovico's most fierce enemies.

Luis XII succeeded where his predecessor had failed, with the conquest of the Duchy of Milan.

Luis entered the city on 6 October 1499. Ludovico the Moor was captured and brought to France.

There he was imprisoned in the tower of Loches (in Berri) where he died in 1510. Under Ludovico the Moor , the city of Milan had a particularly rich flourishing of cultural life, thanks to Ludovico's wish to employ at his Court as many prominent literary men and artists as possible.

Among them, Leonardo Da Vinci, who arrived in Milan in 1482, and created masterpieces of inestimable value during his stay.

In 1490 Ludovico the Moor married Beatrice d'Este, daughter of Duke of Ferrara Ercole I. She bore him sons Massimiliano (1491-1530) and Francesco (1495-1535) who, between 1512 and 1535, conquered back the Duchy of Milan.

Beatrice died in 1497, while giving birth to a child who didn't survive.

Among Ludovico's other children, whom he then had from Lucrezia Crivelli, is Giovanni Paolo, founder of the Marquisate of Caravaggio.