Born in 1542 as the third son of Hojo Ujiyasu, third head of the Later Hojo clan. Around 1556 he was adopted into the family of Oishi Sadahisa, lord of Takiyama Castle in Musashi, taking the name Oishi Genzo Ujiteru and inheriting the Yui domain; he entered Yui Castle (later Takiyama Castle) in 1559. In 1562 he absorbed the former Katsunuma territory of the Mita clan, making him the Hojo's forward base toward northern Musashi and Shimotsuke. During the 1564 Hojo campaign into Shimotsuke, records show troops were mustered at Taki-no-jo Castle (present-day Tokorozawa, Saitama), a satellite fortress of Takiyama. After Takiyama Castle came under attack from Takeda Shingen's forces in 1569, he pushed forward construction of the more formidable Hachioji Castle and relocated his base there. He led Hojo campaigns to capture Sekiyado Castle and various castles in Shimotsuke, but in 1590 he held out at Odawara Castle during Toyotomi Hideyoshi's siege. After the castle's surrender, he was ordered to commit seppuku alongside his brother Ujimasa on July 11, dying at age 49.

He combined the leadership needed to command the retainers of his adoptive Oishi family with an assertive, martial temperament that drove aggressive campaigns toward Shimotsuke and Kozuke. Among the Hojo clan's senior members, he was especially capable in both military and diplomatic affairs.

Known as a master castle-builder who constructed two massive mountain fortresses, Takiyama and Hachioji. The ruins of Hachioji Castle survive today as a National Historic Site, and his death alongside his brother at the fall of Odawara is remembered as an emblematic episode in the collapse of the Later Hojo clan.