Fluridone is an aquatic herbicide commonly used to treat invasive freshwater plant species such as Eurasian watermilfoil, hydrilla, and curly-leaf pondweed. However, required exposures times are very long and often exceed 100 days. Thus, understanding the mechanisms that determine the fate of fluridone in lakes is critical for supporting effective herbicide treatments and minimizing impacts to non-target species. We use a combination of laboratory and field studies to quantify fluridone photodegradation, as well as sorption and microbial degradation in water and sediment microcosms. Laboratory irradiation studies demonstrate that fluridone is susceptible to direct photodegradation with negligible indirect photodegradation, with predicted half-lives in sunlight ranging from 2.3 days (1 cm path length) to 118 days (integrated over 1 meter). Biodegradation is attributable to microbes in sediment with an observed half-life of 57 days. Lastly, fluridone sorbs to sediments (Koc = 340 ± 28 L kg-1); sorption accounts for 16% of fluridone loss in the microcosm experiments. While the laboratory results indicate that all three loss pathways can influence fluridone fate, these controlled studies oversimplify herbicide behavior due to their inability to replicate field conditions. Fluridone concentration measurements in a lake following commercial application demonstrate a half-life of >150 days, indicating that the herbicide is very persistent in water. This study illustrates why caution should be used when relying on laboratory studies to predict the fate of pesticides and other polar organic compounds in the environment.