As a desert park, only a few places in Big Bend support fish. The Rio Grande, and its two tributaries Tornillo and Terlingua Creeks are the only inhabited locations. Although catfish (blue, channel, and flathead) are commonly caught in the Rio Grande, most of the park's 40 species of fish are minnow sized. One of the most famous of these is the endangered Big Bend Gambusia, or Big Bend Mosquitofish (Gambusia Gaigei) which is found only within one tiny spring-fed pond near Rio Grande Village. This is the smallest geographic range of any known vertebrate.

Sadly, we have seen a decline in populations of fish along the Rio Grande in recent years. Two species of fish that had once inhabited the river have not been seen since shortly after the creation of dams upstream and downstream. The last American Eel (Anguilla rostrata) was taken from the Rio Grande near Castolon in 1954; later the last Atlantic sturgeon (Acipenser oxyrhynchus) was taken in the lower canyons. In both cases the fish were dependant on traveling to the ocean in order to breed and it would appear that large impoundments have become their misfortune.

Fishing permits are required to fish in Big Bend and are available at any visitor center.