The Reelfoot rift is the most active of six Iapetan rifts and grabens in central and eastern North America. In contrast, the Rough Creek graben is one of the least active, being seismically indistinguishable from the central craton of North America. Yet the rift and graben adjoin. Hazard assessment in the rift and graben would be aided by identification of a boundary between them. Changes in the strikes of single large faults, the location of a Cambrian transfer zone, and the geographic extent of alkaline igneous rocks provide three independent estimates of the location of a structural boundary between the rift and the graben. The boundary trends north-northwest through the northeastern part of the Fluorspar Area Fault Complex of Kentucky and Illinois, and has no obvious surface expression. The boundary involves the largest faults, which are the most likely to penetrate to hypocentral depths, and the boundary coincides with the geographic change from abundant seismicity in the rift to sparse seismicity in the graben. Because the structural boundary was defined by geologic variables that are expected to be causally associated with seismicity, it may continue to bound the Reelfoot rift seismicity in the future.