When the Kamakura bakufu was overthrown by the army raised byTakauji ASHIKAGA and Yoshisada NITTA in 1331 (Genko War), Yorisada sided with Takauji, and later distinguished himself in various battle fields in cooperation with Takauji during the period of the Northern and Southern Courts (Japan), then he was finally appointed as Mino no Shugo (the provincial constable of Mino Province).
元弘元年（1331年）、足利尊氏、新田義貞らの挙兵によって鎌倉幕府が滅亡した時（元弘の乱）には頼貞は尊氏に味方し、その後の南北朝時代(日本)でも尊氏とともに転戦して戦功をあげ、美濃守護に任じられた。