Recent years have seen the development of a range of approaches concerned with theorizing and empirically demonstrating the significance of “transboundary entanglements” – patterns of connections between and across social sites. This work, spanning disciplines from sociology to international relations, and including subfields from postcolonial scholarship to global history, seeks to transcend the methodological nationalism associated with much preexisting historical social science by examining how, and with what effect, transboundary entanglements are formed and transformed over time. To date, however, the rich theoretical and substantive contributions made by these approaches have not been matched by comparable attention to the methodological principles and transposable procedures that can be used to analyze transboundary entanglements. This article contributes to this task. We make the case for a principle we call “global methodological relationalism” and explore how this principle can be operationalized through a three-step procedure: first, track relations across a boundary; second, follow these relations over time and across cases to establish variation; and third, provide an explanation of this variation. We highlight sites of overlap and contrast with existing methods for case selection, tracing historical processes, and making causal claims in small-N research, and establish the ways in which a “global historical sociology” oriented around “global methodological relationalism” can assess the significance of “transboundary entanglements.”