In the eleventh century the city regained its importance and began to impose its power. Milan became a prosperous, if seldom quiet, comune. The eleventh century saw the birth and growth of several papal and church reform movements, such as the Peace and Truce of God and the Gregorian reforms. Milan itself, the powerful but corrupt church was put under siege by the reformers of the so-called pataria, a local movement led by both religious and secular figures. In the latter half of the century, Milan and its province suffered ecclesiastical schism and confusion as well as violence and war as the patarini struggled to reform the clergy. With peace and order attained in the early 1090s, Milan enterred the wider struggle between the power of the popes and the emperors.

In the twelfth century, she led the other Italian cities in gaining semi-independence from the Holy Roman Empire in the wars of the Lombard League against Frederick Barbarossa, culminating in the glorious Battle of Legnano (1176). Thus, during the Middle Ages Milan became one of the most rich and powerful cities of Europe (due to its commerce and industries) conquering and influencing at times great part of northern Italy. At the beginning of the 11th Century, Milan experienced several civil outbreaks. The main conflicts were between the Nobles and the commoners, who found a religious expression in the Pataria movement. Therefore, a tripartite polity was formed, creating a compromise between the great nobles, lesser nobles, and plebeians, led by a podestà. There was also fighting between the Guelphs and Ghibellines, who supported the pope and emperor respectively. The ruling family of Milan, the Viscontis, supported the Ghibellines, and the emperor acknowledged Ottone Visconti as the Archbishop. The Visconti House went on to peacefully conquer Pavia, Piacenza, Bergamo, Brescia, and Parma.

In 1354, power fell into the hands of brothers Galeazzo and Bernabò Visconti. Originally they split the city in two to share the power, but rejoined in 1359 to defeat Pavia. Pavia then became Galeazzo's city, where be built a university. When he died in 1387, he left his land to his son, Gian Galeazzo Visconti. However, Bernabo was a different child. He ruled under strict laws, was threatened with excommunication, and became greedy after his brother's death. In 1385, when he attempted to take all the land back under one rule, Gian Galeazzo imprisoned him. Gian Galeazzo went on to be a powerful ruler, who expanded his empire across northern Italy and even into Tuscany, gathering land as he went. The only northern city-state to avoid his conquest were Venice and Florence; near this last city he died from illness in 1402 while trying to subdue it. Gian Galeazzo's sons, Giovanni Maria Visconti and Filippo Maria Visconti split up the land, which then either became independent or was conquered by Venice. Giovanni became duke, but in 1412 was assassinated amid political controversy. Filippo had no sons, ending the Visconti line. He died in 1447, when a popular government was established.

Filippo did have a daughter, who married Francesco Sforza, a renowned condottiero. He later was hired to protect the city state with the creation of the popular government, but instead took over, creating the Sforza line. Francesco died in 1466, leaving the land to Galeazzo Maria Sforza. He was disliked because of his cruelty, and assassinated in 1476. His 7-year-old son, Gian bGaleazzo Sforza, with Galeazzo Maria's brother, Ludovico Sforza (Ludovico the Moor), becoming the de facto ruler of Milan. Ludovico was a learned man, adding much to universities and architecture, but when Gian Galeazzo married Princess Isabella of Naples, Ludovico's persuasion of Gian Galeazzo came to an end. Isabella disliked the amount of power Ludovico had, and turned to her family in Naples for help. In return, Ludovico turned to Charles VIII of France, who could claim Naples through the House of Anjou.