The invasive Asian clam Corbicula fluminea was introduced to North America in the 1930s and now inhabits most regions of the conterminous United States; however, the distribution and ecology of C. fluminea in the Columbia River Basin is poorly understood. During 2013 and 2014, 5 Columbia-Snake River reservoirs were sampled monthly from May through September, along with 23 additional lakes and reservoirs sampled once each summer. Associations among C. fluminea veligers, other components of the plankton, and environmental variables were analyzed using non-metric multidimensional scaling and canonical correspondence analysis. Corbicula fluminea veligers were found in high abundances in all mainstem Columbia-Snake River reservoirs, with an annual mean abundance of 71.2 individuals per cubic meter (inds./m³). Only 3 of 23 lakes and (non-mainstem) reservoirs contained C. fluminea, with abundances considerably lower (maximum = 21.2 inds./m³) than in the mainstem reservoirs. A diatom-dominated community preceded the spawning of C. fluminea in early summer at all sites. Corbicula fluminea veligers characterized the plankton community in late summer and were associated with cyanobacteria and high water temperatures. A third community, characterized by cyanobacteria, was apparent in non-mainstem sites in July and August. Our analyses describe the relationship of C. fluminea to the plankton community and environment, which contributes to our understanding of the possible effects of C. fluminea infestations and which waterbodies in the Columbia River Basin are at risk for infestation. Understanding the effects and environmental determinants of invasive mollusks will be increasingly important in the future with the possible arrival of zebra (Dreissena polymorpha) or quagga (D. bugensis) mussels to the region.