The federally endangered humpback chub Gila cypha in the Colorado River within Grand Canyon is currently the focus of a multiyear program of ecosystem-level experimentation designed to improve native fish survival and promote population recovery as part of the Glen Canyon Dam Adaptive Management Program. A key element of this experiment was a 4-year effort to remove nonnative fishes from critical humpback chub habitat, thereby reducing potentially negative interactions between native and nonnative fishes. Over 36,500 fish from 15 species were captured in the mechanical removal reach during 2003–2006. The majority (64%) of the catch consisted of nonnative fish, including rainbow trout Oncorhynchus mykiss (19,020), fathead minnow Pimephales promelas (2,569), common carp Cyprinus carpio (802), and brown trout Salmo trutta (479). Native fish (13,268) constituted 36% of the total catch and included flannelmouth suckers Catostomus latipinnis (7,347), humpback chub (2,606), bluehead suckers Catostomus discobolus (2,243), and speckled dace Rhinichthys osculus (1,072). The contribution of rainbow trout to the overall species composition fell steadily throughout the study period from a high of approximately 90% in January 2003 to less than 10% in August 2006. Overall, the catch of nonnative fish exceeded 95% in January 2003 and fell to less than 50% after July 2005. Our results suggest that removal efforts were successful in rapidly shifting the fish community from one dominated numerically by nonnative species to one dominated by native species. Additionally, increases in juvenile native fish abundance within the removal reach suggest that removal efforts may have promoted greater survival and recruitment. However, drought-induced increases in river water temperature and a systemwide decrease in rainbow trout abundance concurrent with our experiment made it difficult to determine the cause of the apparent increase in juvenile native fish survival and recruitment. Experimental efforts continue and may be able to distinguish among these factors and to better inform future management actions.