Anthropogenic environmental changes may affect habitat suitability for wildlife. Currently, the commercial plantation of non-native trees is one of the most important types of land-use worldwide. The Lower Paraná River Delta in Argentina is a macromosaic of wetlands of high biodiversity value, which has been modified by the afforestation with Salicaceae species. In this context, the Neotropical otter, Lontra longicaudis (classified as Near Threatened at world level and as Endangered in Argentina), faces new challenges related to the colonization of these afforestation landscapes. On this basis, we investigated whether these human-made habitats could be a suitable habitat for the Neotropical otter. We analyzed habitat use and selection by this species at two scales of perception (micro- and macrohabitat) and in two contrasting seasons (winter and summer). Our results show that drainage channels within the afforestation landscape provide suitable conditions for this species during winter. The most important variables at macrohabitat level (dissolved oxygen, pH, and electric conductivity) and seasonally (temperature and pH) appeared to be related to prey availability in the watercourse stretches. At the microhabitat level, the primary factor for distinguishing between used and available sites was soil hardness, possibly related to favorable edaphic conditions for digging burrows. Therefore, the survival of this species in the area will depend on the afforestation management, mainly on those actions that decrease dissolved oxygen levels of waters and increase soil hardness of banks. Under the current wetland loss scenario in the region, afforestation systems may contribute to the conservation of this species.