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The Columbia River Estuary (CRE) on the Pacific coast of North America is a highly modified river-dominated estuary. Land use, development and tributary input vary spatially along the length of the estuary, which may impact the distribution of zooplankton; however the interannual, seasonal and spatial variability of zooplankton have not been evaluated along the tidally-influenced length of the CRE, which extends 234 river kilometers (rkm) inland. To evaluate zooplankton distribution and dynamics along the estuarine gradient, zooplankton and environmental data were collected monthly from five sites spread along 193 rkm (82%) of the estuary over a 2-year period (2016 - 2018). We found that zooplankton abundance and assemblage structure exhibited strong seasonal dynamics. On an interannual basis, abundance was higher in the year with lower river discharge, but there was little variability in assemblage structure between years. At the only saline site sampled near the river mouth, taxa richness and Shannon-Wiener diversity were lower, and assemblages were comprised of greater proportions of estuarine and marine taxa relative to tidal freshwater sites. Zooplankton assemblages at the river mouth were associated with salinity, discharge and temperature, while assemblages at tidal freshwater sites were associated with temperature and season. Non-native taxa, notably the calanoid copepod Pseudodiaptomus forbesi, comprised over 50% of zooplankton abundance at freshwater sites during late summer - early autumn, but were largely absent at the river mouth. Assemblages were highly similar among freshwater sites despite differences in land use and development along the estuarine gradient. Our findings suggest that low residence times in river-dominated estuaries, such as the CRE, may contribute to homogenization of zooplankton assemblages, particularly within the tidal freshwater reach.