On December 15, 1818, the Territory of Missouri created Pulaski County.  The same day, Clark and Hempstead Counties were also created.

The original Pulaski County includes both the present day entity bearing that name as well as all or part of Crawford County and Conway County (both created in 1820), Jefferson County (created in 1829), Scott County (created in 1833), White County (created in 1835), Saline County (created in 1835), Prairie County (created in 1846), Faulkner County (created in 1873), and Lonoke County (created in 1873).  Today, Pulaski County comprises 771 square miles.

The first County government met on May 24, 1819. It met at the home of Samuel McHenry, the first Pulaski County Judge.

Fourteen years after creating a Pulaski County in what is now Arkansas, the State of Missouri created its own Pulaski County.