Sespe Creek is located in the southern Los Padres National Forest in Ventura County, Southern California. The stream winds over 31 miles (50 km) through the Sierra Madre Mountains and Topatopa Mountains, foothills and valleys, and very narrow canyons and gorges.

Sespe Creek's headwaters are in Portero Seco of the Sierra Madre Mountains, and are formed by more than thirty tributary streams in those and the Topatopa Mountains, before its confluence with the Santa Clara River, in Fillmore. Sespe Creek is a National Scenic Waterway and is one of the longest creeks untouched by dams or cement channels. The Sespe Wilderness Area protects a portion of its watershed and channel.

The Sespe Creek watershed is known for the 53,000-acre (210 km²) Sespe Condor Sanctuary. Established in 1947, it is where the critically endangered species California condor (Gymnogyps californicus) has been re-introduced.

At least twelve native and introduced fishes can be found in the creek:

• Arroyo chub – Gila orcuttii
• Pacific lamprey – Entosphenus tridentatus
• Prickly sculpin – Cottus asper
• Santa Ana sucker – Catostomus santaanae
• Steelhead trout – Oncorhynchus mykiss irideus
• Three-spined stickleback – Gasterosteus aculeatus
• Green sunfish – Lepomis cyanellus (introduced)
• Fathead minnow – Pimephales promelas (introduced)
• Black bullhead – Ameiurus melas (introduced)
• Mosquitofish – Gambusia affinis (introduced)
• Golden shiner – Notemigonus crysoleucas (introduced)
• Threadfin shad – Dorosoma petenense (introduced)
• Rainbow trout – Oncorhynchus mykiss (introduced)

A common fish in Sespe Creek is the threespine stickleback (Gasterosteus aculeatus), which is easily identified by its three dorsal spines.

The Pacific lamprey (Entosphenus tridentatus) enters Sespe Creek from the Santa Clara River, which flows into the Pacific Ocean.

The arroyo chub (Gila orcuttii) is often found in schools. The Santa Ana sucker (Catostomus santaanae) is common around waterfalls.

The introduced species, green sunfish (Lepomis cyanellus), can be found in shallow, weedy areas.

• California chaparral and woodlands
• Fauna of the California chaparral and woodlands
• California montane chaparral and woodlands
• Riparian zone