Climate change and landscape transformation have led to rapid expansion of peri-urban areas globally, representing new ‘laboratories’ for the study of human–nature relationships aiming at land degradation management. This paper contributes to the debate on human-driven land degradation processes by highlighting how natural and socioeconomic forces trigger soil depletion and environmental degradation in peri-urban areas. The aim was to classify and synthesise the interactions of urbanisation-driven factors with direct or indirect, on-site or off-site, and short-term or century-scale impacts on land degradation, focussing on Southern Europe as a paradigmatic case to address this issue. Assuming complex and multifaceted interactions among influencing factors, a relevant contribution to land degradation was shown to derive from socioeconomic drivers, the most important of which were population growth and urban sprawl. Viewing peri-urban areas as socio-environmental systems adapting to intense socioeconomic transformations, these factors were identified as forming complex environmental ‘syndromes’ driven by urbanisation. Based on this classification, we suggested three key measures to support future land management in Southern European peri-urban areas.