Background: Feral swine (Sus scrofa) are highly invasive and threaten animal and public health in the Americas. Screwworm (Cochliomyia hominivorax) is listed by the World Organization for Animal Health as a notifiable infestation because myasis cases affect livestock, wildlife, and humans in endemic areas, and outbreaks can be of high socioeconomic consequence in regions where screwworm was eradicated. However, a knowledge gap exists on screwworm infestation of feral swine in South America, where screwworm is endemic. Here, we report infestation with screwworm in feral swine harvested in the Department of Artigas, where the Republic of Uruguay shares borders with Brazil and Argentina. Methods: Myiasis caused by the larvae of screwworm were identified in feral swine with the support and collaboration of a local feral swine hunting club over a three-year period in the Artigas Department of Uruguay. Harvested feral swine were examined for the presence of lesions where maggots causing the myiasis could be sampled and processed for taxonomic identification. The sites of myiasis on the body of infested feral swine and geospatial data for each case were recorded. Feral swine sex and relative size were recorded. Temperature and precipitation for the region were obtained from public sources.Results: Myiases caused by screwworms were recorded in 27 of 618 feral swine harvested. Cases detected in males over 40 kg were associated with wounds that, because of their location, were likely caused by aggressive dominance behavior between adult males. The overall prevalence of screwworm infestation in feral swine was associated with ambient temperature, but not precipitation. Case numbers peaked in the warmer spring and summer months. Conclusions: This is the first report for South America of myasis caused by screwworm in feral swine. In contrast to myasis in cattle that can reach deep into host tissues, screwworms in feral swine tended to cause superficial infestation. The presence of feral swine is a challenge to control screwworms in endemic areas. Screwworm populations maintained by feral swine may contribute to human cases in rural areas of Uruguay, which highlights the One Health importance of this invasive host species-ectoparasite interaction.