Background: Wastewater treatment plants are known as major sources for the release of micropollutants and bacteria into surface waters. To reduce this contaminant and microbial input, new technologies for effluent treatment have become available. The present paper reports the chemical, microbiological, biochemical, and biological effects of upgrading a wastewater treatment plant (WWTP) with a powdered activated carbon stage in the catchment area of the Schussen River, the largest German tributary of Lake Constance. Data were obtained prior to and after the upgrade between 2011 and 2017. Results: After the upgrading, the release of antibiotic resistant and non-resistant bacteria, micropollutants, and their effect potentials was significantly lower in the effluent. In addition, in the Schussen River downstream of the wastewater treatment plant, reduced concentrations of micropollutants were accompanied by both a significantly improved health of fish and invertebrates, along with a better condition of the macrozoobenthic community. Conclusions: The present study clearly provides evidence for the causality between a WWTP upgrade by powdered activated carbon and ecosystem improvement and demonstrates the promptness of positive ecological changes in response to such action. The outcome of this study urgently advocates an investment in further wastewater treatment as a basis for decreasing the release of micropollutants and both resistant and non-resistant bacteria into receiving water bodies and, as a consequence, to sustainably protect river ecosystem health and drinking water resources for mankind in the future.