Doña Ana County is located in the southern part of the State of New Mexico, United States. As of the 2020 U.S. Census, its population was 219,561, which makes it the second-most populated county in New Mexico. Its county seat is Las Cruces, the second-most populous municipality in New Mexico after Albuquerque, with 111,385 as of the 2020 U.S. Census.

Las Cruces is the second-most populous city in the U.S. state of New Mexico and the seat of Doña Ana County. As of the 2020 census the population was 111,385. Las Cruces is the most populous city in both Doña Ana County and southern New Mexico. The Las Cruces metropolitan area had an estimated population of 213,849 in 2017. It is the principal city of a metropolitan statistical area which encompasses all of Doña Ana County and is part of the larger El Paso–Las Cruces combined statistical area with a population of 1,088,420 making it the 56th largest combined statistical area in the United States.