The colonization of the Caribbean initiated a process of entanglement of people, goods, and ideas between the "New" and "Old World," which is popularly referred to as the Columbian Exchange. This paper seeks to highlight the multiscalar and material underpinnings of this process of global importance by tracing it to its roots: the earliest encounters between the indigenous peoples of the Caribbean and European colonists. We present a database, based on key Spanish historical sources, which catalogs all references to the transaction of objects between Amerindians and Europeans from AD 1492-1497. We furthermore argue for the need of a framework that is able to connect, explore, and track the structural materiality of things in encounter events. For this we suggest a combination of entanglement theory with network and substantive analyses. This multiscalar theoretical and methodological framework shows how a diverse and contextually specific network of humans and things arose in tandem with European and Amerindian attempts to establish, manipulate, and contest ties of significant personal and historical interest.