Cyanotoxin pollution is a radical phenomenon involving depth of water bodies, nutrient enrichment, and dominance of cyanobacterial species. This investigation presents a novel framework for assessing cyanotoxin (MC-LR) risk analysis in the north bank plains of Brahmaputra valley, Assam, Northeast India and cyanotoxin pollution was assessed in seven sub-tropical shallow lakes in Tezpur, Sonitpur, Assam. A positive association was established between cyanotoxin pollution and lake trophic state fluctuations. MicrocystinLR (MC-LR) was quantified through a two-way analytical approach involving ELISA and HPLC methods, and the pathways of eutrophication were systematically evaluated involving CNP dynamics and limnological variables. MC-LR was detected in the seven lakes, 1.12–3.46 ppb (HPLC-method) and 1.143–19.42 ppb (ELISA-method); all lakes contained MC-LR beyond WHO permissible limits (>1 ppb). Trophic State Index (TSI) ranged between 52.05–64.59, eutrophic in four lakes and hypereutrophic in three lakes. CNP enrichment boosted algal density, chlorophyll-a, and hence MC-LR in the lakes (p < 0.05; p < 0.01). Secchi Disk Depth (SDD) had significant correlation with TSI and MC-LR potentially released by Microcystis, Dolichospermum, and Nostoc (p < 0.01); MC-LR showed substantial associations with CNP and TSI (p < 0.01). There are current or past records of MC-LR related epidemiological interventions in the study area. Therefore, this study addresses an urgent necessity to monitor cyanotoxin pollution and address the ecotoxicological concerns of harmful algal blooms (HABs) releasing cyanotoxins Northeast India lakes. Risk analysis and risk mitigation following “state of the art” cyanotoxin guidelines will facilitate systematic remediation of cyanotoxin pollution universally.