Drought, land degradation, and desertification are global problems which involve different climatic, soil, vegetation, agricultural and demographic factors. Originally attributed to the most arid regions of the world, the risk of desertification has rapidly increased in temperate regions. In Mediterranean Europe, high human pressure, climatic changes, and intensive agriculture development has combined to produce land consumption, a key factor in starting desertification processes. Unfortunately, the effect of agriculture on land degradation has been poorly considered as far as quantitative indicators and cartographic tools are concerned. The aim of this paper is to introduce a system of agro-environmental indicators aimed at improving a model for desertification risk assessment, especially focusing on land quality, farm management and the impact of agricultural practices. Based on a multivariate exploratory strategy including non-hierarchical cluster analysis and linear discriminant analysis, thirty-two indicators have been included in an Environmentally Sensitive Area (ESA) application to define the contribution of agriculture to land sensitivity in the Region of Lazio (Latium), Italy. Finally, new findings achieved in the context of the agricultural impact on the environment have been discussed as an original contribution to the study of desertification.