San Luis is a city in Yuma County, Arizona, United States. The population was 35,257 at the 2020 census. It is part of the Yuma Metropolitan Statistical Area. San Luis, located in the southwest corner of the state directly adjacent to Mexico's Federal Highway 2 at San Luis Rio Colorado, was the second fastest-growing city or town in Arizona from 1990 to 2000. According to 2022 Census Bureau estimates, the population of the city is 35,770.