AbstractSouthern Europe is a hotspot for desertification risk because of the intimate impact of soil deterioration, landscape transformations, rising human pressure, and climate change. In this context, large-scale empirical analyses linking landscape fragmentation with desertification risk assume that increasing levels of land vulnerability to degradation are associated with significant changes in landscape structure. Using a traditional approach of landscape ecology, this study evaluates the spatial structure of a simulated landscape based on different levels of vulnerability to land degradation using 15 metrics calculated at three time points (early-1960s, early-1990s, early-2010s) in Italy. While the (average) level of land vulnerability increased over time almost in all Italian regions, vulnerable landscapes demonstrated to be increasingly fragmented, as far as the number of homogeneous patches and mean patch size are concerned. The spatial balance in affected and unaffected areas—typically observed in the 1960s—was progressively replaced with an intrinsically disordered landscape, and this process was more intense in regions exposed to higher (and increasing) levels of land degradation. The spread of larger land patches exposed to intrinsic degradation brings to important consequences since (1) the rising number of hotspots may increase the probability of local-scale degradation processes, and (2) the buffering effect of neighbouring (unaffected) land can be less effective on bigger hotspots, promoting a downward spiral toward desertification.