An understanding of land use change and its drivers in semi-arid Mediterranean agro-ecosystems is important for informing ways to facilitate adaptation to future environmental and socioeconomic pressures. In this paper, we mapped and quantified land use changes in the semi-arid Mediterranean agro-ecosystem of Torrealvilla catchment between 1956 and 2008. Subsequently, we detected signs of landscape fragmentation and examined the relationship between land use change trajectories and a set of biophysical factors using Generalized Additive Models (GAMs). Finally, we qualitatively evaluated the role of socioeconomic drivers on the land use change trajectories. The study provides accounts of multidirectional land use trajectories in semi-arid Mediterranean landscapes. Our analysis shows that more than 72% of the study area has undergone significant changes over the past five decades with pronounced effects on landscape composition and structure. Both biophysical and socioeconomic factors are strongly related to the observed spatial and temporal changes in land use. Three major trajectories were observed. Firstly, rain-fed agriculture is becoming less dominant; future abandonment of rain-fed agriculture should be anticipated. Secondly, expansion of forested areas is evident in higher altitudes. The trend is still likely to continue given the possibility of further abandonment of rain-fed farming and existing subsidies for reforestation of arable land. Thirdly, intensification has been observed which has occurred mainly in lower parts of the landscape on flat to gentle slopes and near main roads. Further intensification is likely to be subject to market drivers, irrigation water availability, and future rural development and agricultural policy. Overall, the study shows that even within a given locality, contrasting land use trajectories can emerge as a result of local responses to multiple drivers of change and these need to be carefully taken into account in future policy development.