Pontotoc County is a county located in the U.S. state of Mississippi. As of the 2020 census, the population was 31,184. Its county seat is Pontotoc. It was created on February 9, 1836, from lands ceded to the United States under the Chickasaw Cession. Pontotoc is a Chickasaw word meaning "land of hanging grapes". The original Natchez Trace and the current-day Natchez Trace Parkway both pass through the southeast corner of Pontotoc County.

The Tupelo Micropolitan Statistical Area is a micropolitan area in northeastern Mississippi that covers three counties—Itawamba, Lee and Pontotoc. As of the 2000 census, the area had a population of 125,251. The population at the 2020 Census was 138,390.