In the face of plans for increased construction of dams and reservoirs in the Mekong River Basin, it is critically important to better understand the primary-producer community of phytoplankton, especially the warm-water cyanobacteria. This is because these algae can serve as the primary source of carbon for higher trophic levels, including fishes, but can also form harmful blooms, threatening local fisheries and environmental and human health. We monitored the dynamics of three cyanobacteria-Synechococcus spp., Microcystis aeruginosa, and Dolichospermum spp.-for two years in nine large lakes and reservoirs in the Mekong River Basin. The densities of these algae were largely system-specific such that their abundance was uniquely determined within individual water bodies. However, after accounting for the system-specific effect, we found that cell densities of Synechococcus spp., M. aeruginosa, and Dolichospermum spp. varied in response to changes in photosynthetically active radiation (PAR), total nitrogen, and water level, respectively. Because both PAR and water level tend to fluctuate concordantly over a wide geographic area, Synechococcus spp., and to a lesser extent Dolichospermum spp., varied synchronously among the water bodies. Sustaining the production of pico-sized primary producers while preventing harmful algal blooms will be a key management goal for the proposed reservoirs in the Mekong Basin.