An important challenge in global-change research is to stimulate short-term transient changes in climate, disturbance regime, and recruitment that drive long-term vegetation distributions. Spatial features (e.g., topographic barriers) and processes, including disturbance propagation and seed dispersal, largely control these short-term transient changes. Here we present a frame-based spatially explicit model (ALFRESCO) that stimulates landscape-level response of vegetation to transient changes in climate and explicitly represents the spatial processes of disturbance propagation and seed dispersal. The spatial model and the point model from which it was developed showed similar results in some cases, but diverged in situations where interactions among neighboring cells (fire spread and seed dispersal) were crucial. Topographic barriers had little influence on fire size in low-flammability vegetation types, but reduced the average fire size and increased the number of fires in highly flammable vegetation (dry grassland). Large fires were more common in landscapes with large contiguous patches of two vegetation types while a more heterogeneous vegetation distribution increased fires in the less flammable vegetation type. When climate was held constant for thousands of years on a hypothetical landscape with the same initial vegetation, the spatial and point models produced identical results for some climates (cold, warm, and hot mesic), but produced markedly different results at current climate and when much drier conditions were imposed under a hot climate. Spruce migration into upland tundra was slowed or prevented by topographic barriers, depending on the size of the corridor. We suggest that frame-based, spatially explicit models of vegetation response to climate change are a useful tool to investigate both short- and long-term transients in vegetation at the regional scale. We also suggest that it is difficult to anticipate when non-spatial models will be reliable and when spatially explicit models are essential. ALFRESCO provides an important link between models of landscape-level vegetation dynamics and larger spatio-temporal models of global climate change.