The Río Simpson flows through the Aysén del General Carlos Ibáñez del Campo Region of Chilean Patagonia, originating east of the Andes and forming the western boundary of the city of Coihaique. The Coihaique River, a tributary of the Simpson, borders the city to the north. In its lower course, the river runs through the Reserva Nacional Río Simpson, roughly paralleling Route CH-240, the road connecting Coihaique with Puerto Aisén and Puerto Chacabuco.

The Reserva Nacional Río Simpson was established in 1984 and covers approximately 41,600 hectares, protecting valleys, rivers, forests, and mountains representative of Andean Patagonia. The reserve was created in response to widespread damage from fires and exploitation that had caused flooding, landslides, and significant erosion in the area. The river separates two sections of the reserve and is accessible from kilometer 37 of the Coyhaique–Puerto Aysén route. Notable tributaries within the reserve include the Cascada de La Virgen and Correntoso rivers.

The Río Simpson has been cited as one of the premier fly fishing destinations in the world — ranked fourth globally — which speaks to the clarity and quality of its waters. The surrounding landscape is representative of Andean Patagonian character, with forested valleys and mountain terrain. The river is named after navy hydrographer Enrique Simpson, who explored the region in the 1870s.

The reserve sits just a short distance northeast of Coyhaique, making it relatively accessible for a protected Patagonian waterway. The proximity of Route CH-240 along much of the river's course through the reserve provides multiple potential access points for paddlers. Given the Patagonian location, weather and water conditions can be variable, and paddlers should plan accordingly for the region's characteristic wind and precipitation patterns.