North Mississippi is a region of the U.S. state of Mississippi consisting of Alcorn, Itawamba, Lee, , Prentiss, Tippah, Tishomingo, and Union counties. These counties have a unique cultural and racial history that distinguishes them from other areas in the state of Mississippi. The combined counties have a population of 267,560 (2010). Tupelo is the largest city in the region, but other notable cities include Booneville, Corinth, New Albany, and .
The region is notable for its hilly terrain and infertile soil that made it unsuitable for cotton farming during the Antebellum period, thus resulting in the region having a relatively small African American population today. During the American Civil War (1861-1865) this region of the state was home to many Union sympathizers. Dramatic poverty continued until the establishment of the Tennessee Valley Authority in 1933. Growth in the manufacturing sector during the 1950s and 1960s provided an economic boom to the region, and today the region benefits from the presence of a large health service industry centered on Tupelo.
The region is the most ancestrally Democratic voting and socially conservative regions in Mississippi, often sending Blue Dog Democrats to the state legislature and United States Congress. Democrat Jamie L. Whitten served the region in the United States House of Representatives from 1941 to 1995, and Travis Childers served as its Congressman from 2008 to 2011. As of 2013, the region is home to both of Mississippi's incumbent United States Senators, Thad Cochran and Roger Wicker.