Lake Winnipeg was coined "Canada's sickest lake" and "the most threatened lake in the World" due to its recurrent algal blooms caused by nutrient-rich water inputs. While conceptual frameworks link bloom occurrence to hydrologic connectivity, data-based validation is lacking. We analyzed 355 multi-year satellite-derived images to quantify phytoplankton biomass in Lake Winnipeg and the timing of runoff activation and hydrologic connectivity in the Lake Winnipeg Watershed. Our analyses reveal that the majority of watershed runoff-producing areas exhibit a strong coupling between runoff activation and hydrologic connectivity: they are proximal to rivers and become hydrologically connected to them multiple times a year. Conversely, a smaller number of runoff-producing areas are located further upslope and connect to rivers much less frequently. The latter act as water gatekeepers by selectively enabling the downstream transfer of runoff from headwater regions. Major blooms in Lake Winnipeg only occur when 50% of the water gatekeepers enable headwater-downstream connectivity during 31.5% (or more) of the spring-fall period. We conclude that an explicit assessment of the timing of runoff activation and hydrologic connectivity serves as a predictor of bloom occurrence and provides new information about the influence of a small number of locations on Lake Winnipeg.