We analyzed monthly boat electrofishing data to characterize the littoral fish assemblages of five regions of the Sacramento-San Joaquin Delta (northern, southern, eastern, western, and central), California, during two sampling periods, 1980-1983 (1980s) and 2001-2003 (2000s), to provide information pertinent to the restoration of fish populations in this highly altered estuary. During the 1980s, almost 11,000 fish were captured, including 13 native species and 24 alien species. During the 2000s, just over 39,000 fish were captured, including 15 native species and 24 alien species. Catch per unit effort (CPUE) of total fish, alien fish, and centrarchid fish were greater in the 2000s compared with the 1980s, largely because of increased centrarchid fish CPUE. These differences in CPUE were associated with the spread of submerged aquatic vegetation (SAV), particularly an alien aquatic macrophyte Egeria densa. Native fish CPUE declined from the 1980s to the 2000s, but there was no single factor that could explain the decline. Native fish were most abundant in the northern region during both sampling periods. Nonmetric multidimensional scaling indicated similar patterns of fish assemblage composition during the two sampling periods, with the northern and western regions characterized by the presence of native species. The separation of the northern and western regions from the other regions was most distinct in the 2000s. Our results suggest that native fish restoration efforts will be most successful in the northern portion of the Delta. Management decisions on the Delta should include consideration of possible effects on SAV in littoral habitats and the associated fish assemblages and ecological processes.