Lake Big Momela, one of the East African soda lakes in Northern Tanzania characterised by highly saline-alkaline conditions, making them inhospitable to a range of organisms, although supporting massive growths of some adapted planktonic microorganisms that serve as food for birds, such as Lesser Flamingo. The temporal dynamics of plankton, with an emphasis on cyanobacteria, were examined in 2007 using morphological traits and ribosomal genetic markers (16S and 18S rRNA). Cyanobacterial genes encoding for hepatotoxins (mcyE and ndaF) were also screened. Rotifers and copepods dominated the zooplankton, whereas cyanobacteria, such as Anabaenopsis elenkinii and Arthrospira fusiformis dominated the phytoplankton community, and these being related to representatives in other East African soda lakes. The cyanobacteria community also showed distinct seasonal patterns influenced by environmental parameters, mainly salinity, pH and nitrate. Significant positive correlations were found between phytoplankton abundance and nitrate concentrations (r = 0.617, p = 0.033). No signals of the hepatotoxin synthetase genes mcyE and ndaF were retrieved from cyanobacteria during the whole year. In general, our data illustrate the presence of rich planktonic communities, including some unique and potentially endemic cyanobacteria.