Born in 1525 as the son of Uesugi Tomooki, head of the Ogigayatsu Uesugi clan. In April 1537, at just 13 years old, he inherited leadership upon his father's death. To counter the rising power of the Later Hojo clan in southern Musashi, he had Jindaiji Castle rebuilt and expanded. That July, however, Hojo Ujitsuna bypassed Jindaiji entirely and attacked the Ogigayatsu Uesugi's main stronghold, Kawagoe Castle, forcing Tomosada to retreat to Matsuyama Castle; Jindaiji Castle lost its strategic value and was abandoned. He continued to resist the Hojo, but on May 19, 1546, his forces were routed by a surprise night attack led by Hojo Ujiyasu at the Battle of Kawagoe, where Tomosada is said to have died at age 22 — a defeat that effectively ended the Ogigayatsu Uesugi line.

A young lord who, at just 13, bore the survival of his clan on his shoulders. Despite his youth, he pushed forward castle construction against the Later Hojo — his family's longtime rival — working to build up defenses with limited time and resources.

Because Jindaiji Castle was abandoned soon after Tomosada's reconstruction, it was never modified by the Later Hojo, leaving it a rare surviving example of Ogigayatsu Uesugi-style castle engineering. It was designated a National Historic Site in 2007.