Mismanaged plastic waste threatens the sustainable development goals of the United Nations in social, economic, and ecological dimensions. In the pollution process, fluvial systems are critical transport paths for mismanaged plastic waste, connecting land areas with oceans and acting as plastic reservoirs and accumulation zones. The complex fluid–plastic particle interaction leads to a strong distribution of transported particles over the entire river width and flow depth. Therefore, a holistic plastic removal approach must consider lateral and vertical river dimensions. This study investigates the conceptual design of a comprehensive river-cleaning system that enables the removal of both floating and suspended litter particles from watercourses withstanding flow variations. The innovative technical cleaning infrastructure is based on a self-cleaning system using rotating screen drum units. In 42 prototype-scale experiments using ten representative plastic particle types (both 3D items and fragments) of five different polymer types, we prove the self-cleaning concept of the infrastructure and define its parameters for the best cleaning performance. Its cleaning efficiency is strongly dependent on the polymer type and shape. The overall cleaning efficiency for 3D items amounts to 82%, whereas plastic fragments are removed less efficiently depending on hydraulic conditions. Adaptions to the prototype can enhance its efficiency.