The wastewater circular economy (WW-CE) represents a solution to improving sanitation coverage and management worldwide. However, the transition to circular wastewater treatment plants (WWTPs) requires facilitation to enhance decision-makers’ understanding of the integral sustainability impacts of the WW-CE. This research implemented a Life Cycle Sustainability Assessment (LCSA), combining Life Cycle Assessment, Social Life Cycle Assessment and Life Cycle Costing with a Multi-criteria Decision Making (MCDM) model to quantify the environmental, social, and economic impacts of different WWTPs technologies. Two real WWTPs (Plant A and Plant B) in Chile have embraced alternative WW-CE configurations, adopting the title Biofactories, and are considered as case studies in this investigation. A comparative LCSA considered the service of a 1,000,000-population equivalent, under three scenarios: wastewater discharge without treatment, conventional WWTPs, and biofactory WW-CE configurations. The results demonstrate that the transition to WW-CEs improved integral sustainability, and decreased integrated environmental, social, and economic impacts by 30% in Plant A, demonstrating better performance in terms environmental and social impacts. However, a 58% decrease in integral sustainability impacts for Plant B was achieved via the economic advantage of the thermal hydrolysis pre-treatment of sludge. The urgent need to adopt sustainable decision-making models to improve sanitation coverage and sustainability performance of the sanitation industry across the globe is discussed. The WW-CE in Chile presents an opportunity for this to be achieved.