This article addresses a critical issue related to the assessment of desertification in the Middle Moulouya Basin in northeast Morocco. This basin is a typical example of many Moroccan areas exposed to biophysical and anthropogenic factors that eventually lead to desertification. However, consistent research on this subject is lacking; with a focus on economically significant regions. This paper adopts the Mediterranean Desertification And Land Use (MEDALUS) model, Which among is among the most efficient and reliable models for assessing desertification in the Mediterranean region. The modelling process relies on several indices determine the extent of land degradation, including climate, vegetation, soil, and human actions which encompass a set of sub-indicators. In this work fourteen sub-indicators, adjusted to local conditions; were analyzed and quantified, then assigned a sensitivity coefficient. Was assigned. An overall desertification sensitivity map was generated by combining the sensitivity levels of these four indices. The results showed that 83% of the study area was at moderate to very high risk of desertification, with the central region being the most critically sensitive. Only 17% of the basin area is considered unthreatened by desertification. The method developed in this study allows not only the detection of the level and extent of desertification sensitivity; but also indicates the underlying factors thus providing decision makers with the informative data and scientific evidence needed to develop and implement efficient protection strategies.Graphical abstractThe MEDALUS model was used to assess the vulnerability of the Middle Moulouya Basin in Morocco to desertification. To achieve this, a variety of data was used to define four main quality indicators: soil, climate, vegetation, and human management, each detailed by 14 sub-indicators. These sub-indicators allow for a more detailed analysis of various factors that influence land degradation. Four maps were produced based on soil quality (SQI), vegetation (VQI), climate (CQI), and management (MQI). All maps were then combined to create a Desertification Sensitivity Index (DSI) map. The results showed that nearly 83% of the basin was affected by desertification, with severity levels ranging from moderate to extreme. This study identifies the main natural and human factors responsible for this situation.