There has been a considerable research effort over the past few decades on better understanding and avoiding the progressive collapse of building structures. As a result, current building codes now include provisions to prevent the occurrence of this phenomenon. Most of these measures rely on providing extensive continuity so that alternative load paths are available to redistribute loads after the initial failure of a component. This form of load redistribution can be an effective way of preventing collapse initiation after the failure of single columns. However, after larger initial failures, continuity can promote rather than prevent failure propagation by enabling collapsing parts to pull down parts of the structure that would otherwise be unaffected. In such situations, dividing the structure into different segments can be a more effective way of isolating an initial failure and preventing its propagation. Nevertheless, implementing a segmentation design strategy that completely interrupts continuity would entail reducing safety under operational conditions and after small initial failures. To overcome these limitations, a fuse-based segmentation design approach can be used to combine the advantages of both continuity and segmentation. Using this approach, buildings are not only designed to have sufficient connectivity to prevent collapse after small initial failures, but they are also designed to segment and isolate collapse after large initial failures. Although it has recently been demonstrated that it is possible to design buildings that perform as intended by the fuse-based segmentation approach, it is still not well understood when the approach can be advantageous. As such, this work makes use of collapse simulations based on the Applied Element Method (AEM) to identify initial failure scenarios in which continuity can contribute to more disproportionate collapse for a specific case study involving a reinforced concrete framed building structure.