Misamis takes its name from an old settlement at the mouth of the Panguil Bay once populated by Subanen, now the city of Ozamiz.

However, as a result of continued raids by Moros from Lanao, the Subanens retreated into the interior and Visayan and Bukidnon settlers occupied the coast.

By 1818, Misamis was organized as a province covering the region from Dapitan in the west, up to Gingoog in the east and as far as Cotabato and Lanao del Sur in the south.

The population of Misamis gradually increased during the 19th century due largely to the influx of settlers from Cebu, Bohol, Siquijor and Negros Oriental and doubled a century later with another influx of settlers from Luzon and other parts of Visayas.

When it was still a part of the district of Cebu, there were twelve Spaniards and nine Filipinos who successively served as "governadore" with Mayor Carabello as the first governor in 1874.