Kawagoe Castle was built in 1457 by Ota Dokan, steward of the Ogigayatsu Uesugi, together with his father Doshin. Dokan devised the interlocking moat-and-bailey layout known as 'Dokan-gakari' and, with Edo Castle and Iwatsuki Castle, laid the foundations of Kanto fortification. Until his assassination by his own lord in 1486, the castle he built remained the linchpin of Ogigayatsu Uesugi rule in the region.

In 1546 Kawagoe Castle was besieged by a coalition of the Yamanouchi and Ogigayatsu Uesugi and the Koga kubo, said to number 80,000. Hojo Ujiyasu, the third Later-Hojo lord, led under 10,000 men and, after lulling the enemy, launched a night attack; coordinating with Hojo Tsunashige inside the castle, he shattered the coalition and killed Uesugi Tomosada. This Battle of Kawagoe, counted among Japan's three great night battles, secured Ujiyasu's control of the Kanto (though contemporary records are sparse and details are debated).