The aims of this study were to investigate the presence, possible sources, and potential ecological risks of synthetic musk fragrances in freshwaters and sediments of the main tributaries of a deep subalpine lake in Northern Italy. The total musk concentrations ranged from few ng L−1 up to values > 500 ng L−1, depending on river characteristics: water flow and the presence of wastewater effluents proved to be the main factors affecting fragrance concentrations. The water flow may indeed dilute fragrance input mainly deriving from treated wastewaters. Good correlations (determination coefficients > 0.60) between synthetic fragrances concentrations and parameters related to anthropogenic impacts confirmed this hypothesis: synthetic fragrances were mainly detected in most polluted rivers crossing urbanized areas. Sediment analysis highlighted accumulation of fragrances in this matrix. Concentrations of synthetic fragrances up to 329 ng g−1 organic carbon were measured in sediments of the most contaminated rivers Boesio and Bardello, which also show the highest nutrient content. The preliminary environmental risk assessment revealed that present levels of synthetic musk fragrances do not pose any risk to the studied environmental compartments. However, a probable medium risk level was evidenced during the dry season in the most contaminated rivers Boesio and Bardello. For these reasons, small rivers draining urbanized watersheds and affected by wastewater effluents should be considered synthetic musk contamination hotspots that warrant further research.