Patagonian lakes are one of the most unexplored aquatic environments on Earth, and little is known about their thermo-hydrodynamics and trophic state. Meanwhile, increasing urbanization and industrialization in their catchments compromise their health. Here, we investigate Lake Llanquihue, one of the Earths great freshwater bodies in Northern Patagonia. Still considered pristine, Llanquihue has experienced recent contamination events along its littoral, whose impacts remain unknown. In response, public and private agencies have started to develop tailor-made monitoring plans to survey Lake Llanquihue waters. However, without comprehensive knowledge of the lake’s functioning, it is impossible to determine the fate and effects of contaminants in the waterbody. Here, we characterize via numerical simulations the basin-scale hydrodynamics of Lake Llanquihue, crucial information for diagnosing the transport of matter within its basin. Aiming at delimiting the zones impacted by harmful effluents, we pose a fundamental question significant to any lake: What is the physical connectivity between two zones of interest within a lake? We address this question by introducing a framework that characterizes the preferential pathways and quantifies the timescale tracers take to stream from one zone to another within a waterbody. This framework is applied to investigate the physical connectivity among urban and rural settlements along Lake Llanquihue shore, finding that a time-persistent, large-scale gyre largely controls the physical connectivity between long-distance littoral regions. Lake managers can utilize the introduced framework to monitor lakes’ health, identify and notify potential risk zones impacted by polluted discharge, and advance toward a sustainable relationship with aquatic systems.