Concentrations of pollutants vary in wastes from different sources. However, existing waste input-output (WIO) models do not take these differing concentrations into account. This article proposes a new category of model, which we are calling a waste input-output model at the substance level (WIOS model). The WIOS model considers variations in waste composition. These variations potentially affect the life cycle inventory of the waste treatment stage. The proposed model is expected to produce more accurate results than existing WIO models that do not consider variations in the composition of wastes. In addition, the proposed model provides a method to trace substances undergoing waste treatment. In this article, use of the WIOS model is illustrated by simulating the overall environmental loads of total organic carbon from wastewater treatment at a facility in Germany. The results show that variations in the composition of wastes entering treatment significantly affect the modeled estimates of total environmental loads caused by wastewater treatment. In addition, the results of the proposed model are different from results given by existing hybrid input-output WIO models that do not consider variations in the composition of wastewater as it undergoes treatment.