In view of recent studies of the historical development and current status of industrial symbiosis (IS), life cycle assessment (LCA) is proposed as a general framework for quantifying the environmental performance of by-product exchange. Recent guidelines for LCA (International Reference Life Cycle Data System [ILCD] guidelines) are applied to answer the main research questions in the IS literature reviewed. A typology of five main research questions is proposed: (1) analysis, (2) improvement, and (3) expansion of existing systems; (4) design of new eco-industrial parks, and (5) restructuring of circular economies. The LCA guidelines were found useful in framing the question and choosing an appropriate reference case for comparison. The selection of a correct reference case reduces the risk of overestimating the benefits of by-product exchange. In the analysis of existing systems, environmentally extended input-output analysis (EEIOA) can be used to streamline the analysis and provide an industry average baseline for comparison. However, when large-scale changes are applied to the system, more sophisticated tools are necessary for assessment of the consequences, from market analysis to general equilibrium modeling and future scenario work. Such a rigorous application of systems analysis was not found in the current IS literature, but would benefit the field substantially, especially when the environmental impact of large-scale economic changes is analyzed.