He took power in Milan in 1265, succeeding his cousin Filippo as Anziano del Popolo ("Elder of the People") and, at the same time, podestà of Como, Novara, Bergamo and Lodi.
The Angevin victory at Benevento of the following year meant a triumph of the Guelphs in Italy; in 1267 the main members of the party met in Milan to renew the league against the new Ghibelline leader, the German Conradin.
After Conradin's death in the battle of Tagliacozzo (1268) and his definitive conquest of southern Italy, Charles of Anjou tried to extend his power to the whole peninsula: Napo refused to support his moves, provoking Angevin revenge in the form of rebellions against him.
In 1269 his brother Raimondo, bishop of Como, was captured by Conrad Venosta von Matsch (a minor vassal of Valchiavenna); Napo intervened and freed him in 1273.
In the same year, after the election of Rudolph of Habsburg as Holy Roman Emperor, Napo switched to the imperial party in order to counter the dominance of Charles of Anjou.