Younger brother of Niwa Ujitsugu, lord of Iwasaki Castle in Owari. During the 1584 Battle of Komaki-Nagakute, with his brother away serving Tokugawa Ieyasu, the 16-year-old Ujishige was left in charge of the castle while confined to a sickbed with smallpox. When forces under Ikeda Tsuneoki and Mori Nagayoshi, fighting for Toyotomi Hideyoshi, approached, he rose to lead the defense, sortied from the main gate, and repelled Ikeda's troops three times before being shot down by Mori's men. All 239 defenders are said to have died alongside him.

Known for rising from a sickbed to lead the defense and for his strong sense of duty in guarding the castle during his brother's absence. Though only 16 at his death, his refusal to surrender the castle to the end has been passed down through generations.

His stand at Iwasaki Castle is credited with delaying Hideyoshi's flanking strike toward Tokugawa territory in Mikawa, contributing to the failure of that operation. Today a reconstructed keep stands at the Iwasaki Castle site in Nisshin City, along with a memorial honoring Ujishige and the other defenders who died there.