The Department of Santa Cruz is located in the eastern part of the country covering 370,621 km2, equivalent to 34% of the total area of Bolivia and thus comprising the largest Department in the country.

Its altitude ranges from 300 to 1,600 meters above sea level.

To the North it limits with the Department of Beni and the Federal Republic of Brazil, to the East with Brazil, to the West with the Departments of Cochabamba and Chuquisaca, and to the South with the Department of Chuquisaca and the Republic of Paraguay. 

The Department of Santa Cruz is characterized geographically by the Andean Range to the West to the tropical forests and savannas to the East.

Santa Cruz is considered the economic center of the country and is primarily dedicated to cattle ranching, sugar cane production, petroleum, soy and timber. Its economic importance has also attracted the migration of people from the highlands as well as other parts of the country who are seeking employment opportunities and a better quality of life.