Epistemology is the main branch of philosophy that studies the nature of knowledge, but how is new knowledge created? In this perspective article, I introduce a novel method of knowledge discovery that synthesizes online findings from current and prior research. This web-based knowledge synthesis method is especially relevant in today’s information technology environment, where the research community has easy access to online interactive tools and an expansive selection of digitized peer-reviewed literature. Based on a grounded theory methodology, the innovative synthesis method presented here can be used to organize, analyze and combine concepts from an intermixed selection of quantitative and qualitative research, inferring an emerging theory or thesis of new knowledge. Novel relationships are formed when synthesizing causal theories—accordingly, this article reviews basic logical principles of associative relationships, mediators and causal pathways inferred in knowledge synthesis. I also provide specific examples from my own knowledge syntheses in the field of epidemiology. The application of this web-based knowledge synthesis method, and its unique potential to discover breakthrough knowledge, will be of interest to researchers in other areas, such as education, health, humanities, and the science, technology, engineering, and mathematics (STEM) fields.