Land use and land cover (LULC) is a powerful driver of sustainable landscape development, conservation and management. This is especially true for Mediterranean agricultural landscapes, which are increasingly sensitive to human activities, water scarcity and climate change. Therefore, this study investigates the patterns, dynamics and driving forces of LULC changes affecting Mediterranean agricultural ecosystems, taking southern Spain (regions of Andalusia and Murcia) as a representative case study. Analysis of LULC change facilitates the design of policies to balance competing uses, development pressures and conservation imperatives. Cartographic modelling of LULC changes was applied using the level-3 44 classes of CORINE Land Cover (CLC) maps for 2006 and 2018. Cross-tabulation techniques and descriptive statistics of land uses (persistence, gains, losses, total change, net change and annual change) have been used. LULC change processes have been geographically localized and correlated with their driving factors using logistic regression modelling. Part of these factors are environmental and biophysical (topography, climate, soils, aquifers, protected areas) whereas others are socioeconomic (accessibility, agricultural and environmental policies, natural resource management plans, urban planning, among others). GUIDOS software has been used to compute a fragmentation index of agricultural landscape that contributes to understanding ecological implications of the LULC changes within agricultural semi-natural ecosystems in the study area. Results indicate inter alia that in both regions over 81,000 hectares of agricultural land have changed their use status toward other non-agricultural uses during 2006-2018 due to diverse processes of LULC change, generating significant socioeconomic and environmental implications. Agricultural lands have experienced inverse processes such as crop intensification and extension of irrigated crops, as well as reduction in rainfed arable land and agroforestry areas. It is expected that the results obtained can help policymakers and managers responsible for agricultural and environmental policies in their decision-making processes, including decisions related to agricultural land management, crop diversification, and allocation of the CAP and the agri-environmental payments. Results also could be useful for other countries holding similar agricultural ecosystems.