In this article, a comparative analysis of Karl Popper’s falsifiability theory and Ludwig Wittgenstein’s theory of meaning in the context of the historical-philosophical approach to the problem of new knowledge formation and justification is undertaken. An assumption is made that the constellation of fact is connected with the possibility of the emergence of an epistemological field. Researchers have repeatedly addressed this issue; however, one important detail received no due attention: Popper’s counter-arguments regarding Wittgenstein’s view on semantic paradoxes show the fundamental difference of these philosophers’ views on the sign and the signified (language and world), which contributes to the analysis of new knowledge formation. Arguments that concern both early and late periods of Wittgenstein’s philosophy are used in this study. The uncertainty of the demarcation criterion (according to Popper) allowed analyzing Wittgenstein’s position as to how and why different rules of inference form different epistemological fields.