The adverse impacts of harmful algal blooms (HABs) are increasing worldwide. Lake Erie is a North American Great Lake highly affected by cultural eutrophication and summer cyanobacterial HABs. While phosphorus loading is a known driver of bloom size, more nuanced yet crucial questions remain. For example, it is unclear what mechanisms are primarily responsible for initiating cyanobacterial dominance and subsequent biomass accumulation. To address these questions, we develop a mechanistic model describing June–October dynamics of chlorophyll a, nitrogen, and phosphorus near the Maumee River outlet, where blooms typically initiate and are most severe. We calibrate the model to a new, geostatistically-derived dataset of daily water quality spanning 2008–2017. A Bayesian framework enables us to embed prior knowledge on system characteristics and test alternative model formulations. Overall, the best model formulation explains 42% of the variability in chlorophyll a and 83% of nitrogen, and better captures bloom timing than previous models. Our results, supported by cross validation, show that onset of the major midsummer bloom is associated with about a month of water temperatures above 20 °C (occurring 19 July to 6 August), consistent with when cyanobacteria dominance is usually reported. Decreased phytoplankton loss rate is the main factor enabling biomass accumulation, consistent with reduced zooplankton grazing on cyanobacteria. The model also shows that phosphorus limitation is most severe in August, and nitrogen limitation tends to occur in early autumn. Our results highlight the role of temperature in regulating bloom initiation and subsequent loss rates, and suggest that a 2 °C increase could lead to blooms that start about 10 days earlier and grow 23% more intense.