Cyanobacterial Harmful Algal Bloom (CyanoHAB) proliferation is a global problem impacting ecosystem and human health. Western Lake Erie (WLE) typically endures two highly toxic CyanoHABs during summer: a Microcystis spp. bloom in Maumee Bay that extends throughout the western basin and a Planktothrix spp. bloom in Sandusky Bay. To investigate nitrogen (N) and phosphorus (P) limitation of biomass and toxin production in WLE CyanoHABs, we conducted in situ nutrient addition and dilution microcosm bioassays in June and August 2019. During the early Sandusky Bay bloom in June, hepatotoxic microcystin and neurotoxic anatoxin production occurred. In June, the Sandusky Bay nutrient addition and dilution bioassays indicated anatoxin production was not solely limited by N or P. During August, the Maumee Bay bloom produced microcystins and the Sandusky Bay bloom produced anatoxin. Production of microcystin by the Maumee Bay bloom was P-limited. Anatoxin production in August 2019 in Sandusky Bay was N limited in both nutrient addition and reduction experiments. The results demonstrate the importance of recognizing spatial heterotrogeneity in aquatic systems and that to properly combat cyanotoxin production in WLE, both N and P reduction efforts should be implemented in its watershed.