Born on the third day of the ninth month of Tenbun 9, Yoshihiro was the third son of Kakizaki Suehiro. While the Kakizaki clan at this date exerted suzerainty over the lords of the local fortified residences on the Oshima Peninsula, they were themselves subordinate to the Andō clan of Tōhoku; moreover, their authority was limited to the Japanese inhabitants of the "Land of the Yamato people, rather than encompassing also the Ainu with whom they traded. After Toyotomi Hideyoshi defeated the Hōjō at Odawara in 1590, and took measures to check the power of the great clans of the north, Yoshihiro travelled to Kyōto, where in the twelfth month of that year he enjoyed an audience with the kampaku at the Jurakudai palace. Reporting on the state of affairs in Ezo, Yoshiro declined a grant of five thousandkoku, but had bestowed upon him Junior Fifth Court Rank, Lower Grade and the office of Minbu Taifu or Senior Vice Minister in the Ministry of Popular Affairs, thus gaining independence from the Andō. Receiving from Hideyoshi also three gorgeous costumes and two hundredryō of silver, he departed again for the north, reaching the Oshima Peninsula in the third month of 1591. Later that year, Yoshihiro sent troops to help suppress the Kunohe Rebellion, the arrows of the contingent of Ainu seeing mention in Mikawa Go-fudoki for their remarkable quality of dealing death even upon the lightly injured. In the eleventh month of the first year of Bunroku, Yoshihiro travelled to Ōsaka, but Hideyoshi was at Hizen Nagoya, in relation to the invasion of Korea; reaching his camp in Kyūshū, as recorded in Shinra no Kiroku, on the second day of the new year Yoshihiro enjoyed another audience with Hideyoshi, where the two discussed Ezo and the invasion. Three days later, Yoshihiro had conferred upon him a red-seal letter affirming his rights to trade with the Ainu. In 1604 he was granted exclusive trading rights with the Ainu by shōgunTokugawa Ieyasu. While neither document conferred specific territorial rights or a "fictive rice income", the Matsumae Domain would generally be treated as equivalent to tozama daimyō with an income of ten thousandkoku. Yoshihiro built Matsumae Castle.
