Phosphorus (P) is one of the key limiting nutrients for algal growth in most fresh surface waters. Understanding the determinants of P accumulation in the water column of lakes of interest, and the prediction of its concentration is important to water quality managers and other stakeholders. We hypothesized that lake physicochemical, climate, and watershed land-use attributes control lake P concentration. We collected relevant data from 126 lakes in Maine, USA, to determine the major drivers for summer total epilimnetic P concentrations. Predictive regression-based models featured lake external and internal drivers. The most important land-use driver was the extent of agriculture in the watershed. Lake average depth was the most important physical driver, with shallow lakes being most susceptible to high P concentrations; shallow lakes often stratify weakly and are most subject to internal mixing. The sediment NaOH-extracted aluminum (Al) to bicarbonate/dithionite-extracted P molar ratio was the most important sediment chemical driver; lakes with a high hypolimnetic P release have low ratios. The dissolved organic carbon (DOC) concentration was an important water column chemical driver; lakes having a high DOC concentration generally had higher epilimnetic P concentrations. Precipitation and temperature, two important climate/weather variables, were not significant drivers of epilimnetic P in the predictive models. Because lake depth and sediment quality are fixed in the short-term, the modeling framework serves as a quantitative lake management tool for stakeholders to assess the vulnerability of individual lakes to watershed development, particularly agriculture. The model also enables decisions for sustainable development in the watershed and lake remediation if sediment quality is conducive to internal P release. The findings of this study may be applied to bloom metrics more directly to support lake and watershed management actions.