The son of the Holy Roman emperor Frederick II, Manfred became vicar of Italy and Sicily for his half brother Conrad IV but soon began seeking the Sicilian crown for himself. On Conrad's death in 1254 a diet at San Germano ignored the imperial representative and elected Manfred. Pope Alexander IV, however, after having excommunicated Manfred twice, invested Edmund, son of Henry III of England, with the Sicilian kingdom in April 1255. A papal army entered the kingdom, but Manfred resisted successfully and was crowned king of Sicily at Palermo on Aug. 10, 1258.

As protector of the Italian Ghibellines, Manfred asserted himself also in Lombardy and Tuscany; and he further strengthened his position by the betrothal, in 1260, of his daughter Constance to the infante Peter of Aragon. Negotiations with the new pope, Urban IV, came to nothing; and Urban, considering Alexander IV's agreement with England void, offered the Sicilian crown to Charles of Anjou, who sailed for Rome in May 1265. Manfred, having failed to prevent Charles's army from joining him, was defeated near Benevento; he fell in battle.