Pharmaceutical pollution poses an increasing threat to global wildlife populations. Psychoactive pharmaceutical pollutants (e.g. antidepressants, anxiolytics) are a distinctive concern owing to their ability to act on neural pathways that mediate fitness-related behavioural traits. However, despite increasing research efforts, very little is known about how these drugs might influence the behaviour and survival of species in the wild. Here, we capitalize on the development of novel slow-release pharmaceutical implants and acoustic telemetry tracking tools to reveal that exposure to environmentally relevant concentrations of the benzodiazepine pollutant temazepam alters movement dynamics and decreases the migration success of brown trout (Salmo trutta) smolts in a natural lake system. This effect was potentially owing to temazepam-exposed fish suffering increased predation compared with unexposed conspecifics, particularly at the river-lake confluence. These findings underscore the ability of pharmaceutical pollution to alter key fitness-related behavioural traits under natural conditions, with likely negative impacts on the health and persistence of wildlife populations.