Physical, chemical, and biological gradients along reservoirs are clear and exhibit marked spatial and temporal variations. These variations are rarely quantified and may produce spatial gradients in fisheries. We analyzed trends in total yield and gradients and relationships between catch-per-unit-effort (CPUE) and some characteristics of the fishery in the large Neotropical Itaipu Reservoir in Brazil. Data on the artisanal fisheries were collected over an 11-year period (414 213 daily trips). Annual yield (especially after 1993) and CPUE (annual total and for each species) decreased over the studied period. A clear longitudinal pattern in the CPUE values for the main species was recognized, and this pattern presented a significant relationship with the type of gear and characteristics of the vessels used in the fisheries. The decline in yield and CPUE is apparently due to changes in trophic state, as well as to the construction of reservoirs upstream from the region and to overfishing. It is clear that the spatial zonation influenced fish species distribution along the reservoir and, therefore, the fishery. We conclude that for this large Neotropical reservoir, spatial gradient cannot be ignored in management plans, and this appears to be true for any reservoir that exhibits zonation.