The 139,577 hectares (538.91 sq mi) reserve is located in the transition of the Nearctic and Neotropical realms and encompasses parts of the Sierra Madre del Sur, with a wide range of altitudes, climates and soils.

The reserve is administered by the municipalities of Autlán, Cuautitlán, Casimiro Castillo, Tolimán and Tuxcacuesco in Jalisco and Minatitlán and Comala in Colima.

The climate in the region is influenced by various factors in addition to its latitudinal location, such as its proximity to the coast, the effect of its landform – orographic shade – and the breadth of the altitudinal range, which partly explains the high regional biodiversity and the presence of numerous plant formations ranging from tropical forests to those of temperate-cold climates.

Eighty-five species of amphibians and reptiles have been recorded; of these it is known that 13 are endemic to the western and central region of Mexico: the rattlesnake, the black iguana, the frog Shyrrhopus modestus, the beaded lizard (Heloderma horridum) and the Autlan rattlesnake (Crotalus lannomi), an endemic species only reported for the area of Puerto de Los Mazos.

[2] As of 2002[update], more than 40,000 people lived in the Sierra de Manantlán, engaged mainly in agriculture (corn, beans, tomatoes, sugarcane, watermelon, mangoes), livestock grazing, timber production, and extraction of wood for fuel and mining of coal or minerals.