One of Uesugi Kenshin's most experienced but most troublesome retainers. His father, Honjou Fusanaga, was the head of the Honjou Clan, but his castle was stolen away by his younger brother Ogawa Nagasuke just before Shigenaga was born. He died soon after. Shigenaga became the head of his clan at a very young age with his uncle as his guardian. Shigenaga was said to have a strong, daring temperment from childhood. On the 13th anniversary of his father's dead, he had his uncle Nagasuke seized and drove him to suicide, thereby taking back the real power of the clan.
Though in the beginning he was hostile towards Nagao Kagetora (Uesugi Kenshin), whom his uncle had supported, he became one of Kenshin's vassals in 1558 and fought in many of his battles, including the Battles of Kawanakajima. However, Shigenaga had a strong tendency towards independence; in 1568 he schemed with Takeda Shingen to declare his independence from Kenshin. The rebellion was put down by Kenshin, and Shigenaga surrendered with the intercession of Ashina Moriuji. His son and heir Honjou Akinaga was given as hostage, and Shigenaga was forgiven.
After Kenshin's death, he initially supported Uesugi Kagetora in the Otate no Ran, but surrendered to Uesugi Kagekatsu and later served him.