When his nephew, Emperor Shomu was enthroned, Fusasaki ousted Nagaya no Okimi who held power as an imperial family member and was also his political rival (Incident of Prince Nagaya), and he took charge of the administration as the pivot of the Fujiwara Four Brothers (also called Fujiwara Four Sons) regime.
甥の聖武天皇即位後、天平元年（729年）に皇親勢力の巨頭で政治上のライバルであった長屋王を失脚させ（長屋王の変）、藤原四兄弟藤原四子政権の中心人物として、藤原四兄弟とともに政権を主導した。