Cuatrocienegas is in the state of Coahuila, about 200 km south of the border city of Piedras Negras and 340 km west of Monterrey. The most straightforward approach from Monterrey is via Highway 53 through Monclova — allow four to five hours. From Saltillo, take Highway 54 north; it's about three hours.
There is no direct commercial flight to Cuatrocienegas. The nearest airports are Monclova (15 km away, limited service) and Monterrey (five hours by road, with good international connections). Public buses from Monclova run to Cuatrocienegas several times a day; the journey takes about half an hour. For visiting the biosphere reserve sites, a rental car or a local taxi hired for the day is the practical option — the pozas and dunes are spread across a large area with no public transport.