San Isabel National Forest is located in central Colorado. The forest contains 19 of the state's 53 fourteeners, peaks over 14,000 feet (4,267 m) high, including Mount Elbert, the highest point in Colorado.

It is one of eleven national forests in the state of Colorado and contains the Sawatch Range, the Collegiate Peaks, and Sangre de Cristo Range. It has a total area of 1,120,233 acres (1,750.364 sq mi; 4,533.42 km²) spread out over parts of eleven counties in central Colorado. In descending order of land area it is located in Chaffee, Custer, Lake, Huerfano, Fremont, Pueblo, Saguache, Las Animas, Park, Costilla, and Summit counties.

San Isabel National Forest is co-managed by the Forest Service together with Pike National Forest, Cimarron National Grassland, and Comanche National Grassland from offices in Pueblo. There are local ranger district offices located in Cañon City, Leadville, and Salida.

There are seven officially designated wilderness areas lying within San Isabel National Forest that are part of the National Wilderness Preservation System. Four of them extend into neighboring National Forests, and of these, one also onto land under management of the National Park Service. Another one extends onto land of the United States Fish and Wildlife Service (as indicated).