The Wyandot tribe settled in the area that would become Wyandotte County, Kansas in 1843, having been removed from Ohio. Quindaro in 1856 was the first townsite created by white settlers after the territory of Kansas opened for settlement, though various traders and frontiersmen had lived in the area for decades prior. Wyandotte County itself was organized in 1859. The city of Wyandot was incorporated when the county was created and was the site of the final state convention to create a constitution for the state of Kansas.

Rosedale was formed in 1872, becoming a city of the third class in 1877 after its population reached over 600. In 1905 the University of Kansas opened the School of Medicine and began providing instruction at Rosedale's Bell Memorial Hospital, the school later moving to 39th Street and Rainbow Boulevard. Rosedale was one of the last cities to be annexed by Kansas City, remaining an independent community until 1922.

Argentine started as Silver City in 1880, when James W. Coburn purchased land to plot a town centered around the creation of a smelter to refine silver ore from throughout North and South America. After the smelter shut down and other financial and physical disasters struck the town, Argentine city leaders began actively seeking annexation from Kansas City, Kansas in the early 20th century. Argentine was annexed by KCK in 1909.

Kansas City, Kansas was formed as a town company in 1868. In 1886 the town was reformed through the merger of 5 cities: Kansas City, Armstrong, Armourdale, Riverview, and Wyandotte. The city became a suburban community for Kansas City, Missouri in the 1890s and continued expanding as other small cities and communities merged into it. In 1997 the Kansas Legislature passed legislation allowing the city government of Kansas City to unify with the county government of Wyandotte.