The Kakegawa area has been regional commercial center within T?t?mi Province since at least the Kamakura period, but developed as a castle town under the Imagawa clan, whose headquarters was in neighboring Suruga Province. Kakegawa Castle was built by Asahina Yasuhiro, a retainer of Imagawa Yoshitada, in the Bunmei era (1469–1487). The castle later fell into the hands of the Tokugawa clan, but was then to Toyotomi clan retainer Yamauchi Kazutoyo in 1580. After the establishment of the Tokugawa shogunate, Kakegawa Domain was created, and ruled by numerous fudai daimy?. The area prospered during the Edo period, as the T?kaid? highway connecting Edo with Kyoto passed through Kakegawa, whose post stations included Nissaka-shuku and Kakegawa-juku. Neighboring Yokosuka Domain, a smaller fudai holding, was also located within what are now the city limits of Kakegawa.
After the Meiji Restoration, Kakegawa was made part of the short-lived Hamamatsu Prefecture in 1871, which merged with Shizuoka Prefecture in 1876. Kakegawa Town was created in the cadastral reform of April, 1891, four years after the opening of Kakegawa Station on what later became the T?kaid? Main Line railway. The town expanded steadily over the years, annexing neighboring villages and towns in Ogasa District, and was elevated in status of that of a city in 1954.
On April 1, 2005 the towns of Dait? and ?suka, both from Ogasa District, were merged into the original Kakegawa