With the increasing occurrence of cyanobacteria blooms, it is crucial to improve our ability to monitor impacted lakes accurately, efficiently, and safely. Cyanobacteria are naturally occurring in many waters globally. Some species can release neurotoxins which cause skin irritations, gastrointestinal illness, pet/livestock fatalities, and possibly additional complications after long-term exposure. Using a DJI M300 RTK Unmanned Aerial Vehicle equipped with a MicaSense 10-band dual camera system, six New Hampshire lakes were monitored from May to September 2022. Using the image spectral data coupled with in situ water quality data, a random forest classification algorithm was used to predict water quality categories. The analysis yielded very high overall classification accuracies for cyanobacteria cell (93%), chlorophyll-a (87%), and phycocyanin concentrations (92%). The 475 nm wavelength, normalized green-blue difference index—version 4 (NGBDI_4), and normalized green-red difference index—version 4 (NGRDI_4) indices were the most important features for these classifications. Logarithmic regressions illuminated relationships between single bands/indices with water quality data but did not perform as well as the classification algorithm approach. Ultimately, the UAS multispectral data collected in this study successfully classified cyanobacteria cell, chlorophyll-a, and phycocyanin concentrations in the studied NH lakes.