Pharmaceuticals, personal care products, hormones, and other chemicals lacking water quality standards are frequently found in surface water. While evidence is growing that these contaminants of emerging concern (CECs) – those previously unknown, unrecognized, or unregulated – can affect the behavior and reproduction of fish and wildlife, little is known about the distribution of these chemicals in rural, tribal areas. Therefore, we surveyed the presence of CECs in water, sediment, and subsistence fish species across various waterbodies, categorized as undeveloped (i.e., no human development along shorelines), developed (i.e., human development along shorelines), and wastewater effluent-impacted (i.e., contain effluence from wastewater treatment plants), within the Grand Portage Indian Reservation and 1854 Ceded Territory in northeastern Minnesota, U.S.A. Overall, in 28 sites across three years (2016–2018), 117 of the 158 compounds tested were detected in at least one form of medium (i.e., water, sediment, or fish). CECs were detected most frequently at wastewater effluent-impacted sites, with up to 83 chemicals detected in one such lake, while as many as 17 were detected in an undeveloped lake. Although there was no statistically significant difference between the number of CECs present in developed versus undeveloped lakes, a range of 3–17 CECs were detected across these locations. Twenty-two CECs were detected in developed and undeveloped sites that were not detected in wastewater effluent-impacted sites. The detection of CECs in remote, undeveloped locations, where subsistence fish are harvested, raises scientific questions about the safety and security of subsistence foods for indigenous communities. Further investigation is warranted so that science-based solutions to reduce chemical risks to aquatic life and people can be developed locally and be informative for indigenous communities elsewhere.