Planktothrix species are distributed worldwide, and these prevalent cyanobacteria occasionally form potentially devastating toxic blooms. Given the ecological and taxonomic importance of Planktothrix agardhii as a bloom species, we set out to determine the complete genome sequence of the type strain Planktothrix agardhii NIES-204. Remarkably, we found that the 5S ribosomal RNA genes are not adjacent to the 16S and 23S ribosomal RNA genes. The genomic structure of P. agardhii NIES-204 is highly similar to that of another P. agardhii strain isolated from a geographically distant site, although they differ distinctly by a large inversion. We identified numerous gene clusters that encode the components of the metabolic pathways that generate secondary metabolites. We found that the aeruginosin biosynthetic gene cluster was more similar to that of another toxic bloom-forming cyanobacterium Microcystis aeruginosa than to that of other strains of Planktothrix, suggesting horizontal gene transfer. Prenyltransferases encoded in the prenylagaramide gene cluster of Planktothrix strains were classified into two phylogenetically distinct types, suggesting a functional difference. In addition to the secondary metabolite gene clusters, we identified genes for inorganic nitrogen and phosphate uptake components and gas vesicles. Our findings contribute to further understanding of the ecologically important genus Planktothrix.