The aim of this study was to determine the amount, composition and origin of plastic debris in one of the world largest river, the Parana River in Argentina (South America), focusing on the impact of urban rivers, relationships among macro, meso and microplastic, socio-political issues and microplastic ingestion by fish. We recorded a huge concentration of macroplastic debris of domestic origin (up to 5.05 macroplastic items per m2) dominated largely by bags (mainly high- and low-density polyethylene), foodwrapper (polypropylene and polystyrene), foam plastics (expanded polystyrene) and beverage bottles (polyethylene terephthalate), particularly downstream from the confluence with an urban stream. This suggests inadequate waste collection, processing and final disposal in the region, which is regrettably recurrent in many cities of the Global South and Argentina in particular. We found an average of 4654 microplastic fragments m-2 in shoreline sediments of the river, ranging from 131 to 12687 microplastics m-2. In contrast to other studies from industrialized countries from Europe and North America, secondary microplastics (resulting from comminution of larger particles) were more abundant than primary ones (microbeads to cosmetics or pellets to the industry). This could be explained by differences in consumer habits and industrialization level between societies and economies. Microplastic particles (mostly fibres) were recorded in the digestive tract of 100% of the studied Prochilodus lineatus (commercial species). Contrary to recently published statements by other researchers, our results suggest neither macroplastic nor mesoplastics would serve as surrogate for microplastic items in pollution surveys, suggesting the need to consider all three size categories. The massive plastic pollution found in the Parana River is caused by an inadequate waste management. New actions are required to properly manage waste from its inception to its final disposal.