Born in 1394 as a younger brother of the fourth shogun Ashikaga Yoshimochi, he had entered the priesthood and become head of the Tendai school. When Yoshimochi died without an heir, Yoshinori was chosen as the sixth shogun by lot (1428). After assuming office he worked energetically to restore shogunal authority, pressuring the Kamakura Kubō Ashikaga Mochiuji and destroying him in the Eikyō Disturbance of 1438. He also moved to reduce the power of the western daimyo, forcibly cutting the domains of powerful lords such as Akamatsu Mitsusuke. The ferocity of his politics earned him the name "Terror of All Men." In 1441 he was invited to a banquet hosted by Akamatsu Mitsusuke and was assassinated there (the Kakitsu Disturbance). He was 48. His authoritarian rule aimed to restore shogunal prestige but provoked the daimyo's resentment and ended in assassination. After his death, shogunal authority declined rapidly.

An autocratic ruler with an intense sense of authority and cold decisiveness. Faced with the need to overcome the stigma of a shogun chosen by lot, he may have adopted ever more forceful policies to compensate. He tried to control his retainers through ruthless purges alternated with generous rewards, but ultimately that very severity brought about his own ruin. He also had an ambitious side that sought to integrate religious authority (his background as Tendai head) with secular power.

The Kakitsu Disturbance, a rare instance of a shogun being assassinated by a retainer, left its mark on history and caused a decisive decline in shogunal authority. The instability among the daimyo that Yoshinori had weakened led to the volatile political situation that produced the Ōnin War of 1467. In recent years his reputation as a reformer who sought to restore shogunal authority through strong rule has also grown.