Tupelo is a city in and the county seat of Lee County, Mississippi, United States. Founded in 1860, the population was 37,923 at the 2020 cen…Tupelo is a city in and the county seat of Lee County, Mississippi, United States. Founded in 1860, the population was 37,923 at the 2020 census. It is the 7th most populous city in Mississippi and is considered a commercial, industrial, and cultural hub of northern Mississippi.