In the early third and fourth centuries respectively, Ammonius of Alexandria and Eusebius of Caesarea engaged in cutting-edge research on the relationships among the four canonical gospels. Indeed, these two figures stand at the head of the entire tradition of comparative literary analysis of the gospels. This article provides a more precise account of their contributions, as well as the relationship between the two figures. It argues that Ammonius, who was likely the teacher of Origen, composed the first gospel synopsis by placing similar passages in parallel columns. He gave this work the title Diatessaron-Gospel, referring thereby to the four columns in which his text was laid out. This pioneering piece of scholarship drew upon a long tradition of Alexandrian textual scholarship and likely served as the inspiration for Origen's more famous Hexapla. A little over a century later, Eusebius of Caesarea picked up where Ammonius left off and attempted to accomplish the same goal, albeit using a different and improved method. Using the textual parallels presented in the Diatessaron-Gospel as his ‘raw data’, Eusebius converted these textual units into numbers which he then collated in ten tables, or ‘canons’, standing at the beginning of a gospel book. The resulting cross-reference system, consisting of the Canon Tables as well as sectional enumeration throughout each gospel, allowed the user to find parallels between the gospels, but in such a way that the literary integrity of each of the four was preserved. Moreover, Eusebius also exploited the potential of his invention by including theologically suggestive cross-references, thereby subtly guiding the reader of the fourfold gospel to what might be called a canonical reading of the four.