Human activities as well as natural events can dramatically affect land degradation negatively or positively. In Egypt, agriculture is a key sector of the economy. Land reclamation seeks to transfer desert areas (New lands) to agricultural land and support the construction of new villages. The agricultural productivity improvement of these new lands is slow and requires considerable time due to their fragility and sensitivity to desertification. The main objectives of this study were the assessment, monitoring, and mapping of the areas' most sensitive to desertification in the Bahariya Oasis depression, Egypt; one of the new lands that was targeted for reclamation. Mediterranean desertification and land use (MEDALUS) approach was modified by adding new variables to the soil (SQI), vegetation (VQI), management (MQI) quality indicators while irrigation water quality (IWQI) was considered as a new indicator. The main goals were achieved via: (a) modifiyng the MEDALUS factors to obtain more reliable data at the local level, (b) identifying the most environmentally sensitive areas to desertification in the study area, c) assessing the environmental sensitivity area index (ESAI) for two time series (1984 and 2017) to determine the effects of land reclamation processes, and (d) monitoring the ESAI change between 1984 and 2017 over the studied area. Five landforms were recognized in the Bahariya Oasis depression which are alluvial plain, lowland, peneplain, plateau and hills, and playa. The ESAI results indicated that the 90.6% of the study area in 1984 was decreased to 44.2% in 2017 due to the impact of reclamation processes and high quality of SQI, MQI, and IWQI. By contrast, playa area as land sensitivity to desertification is increased from 15 km2 in 1984 to 25 km2 2017, highlighting the necessity of substantial mitigation policies. Since the Baharyia Oasis is intensively cultivated, more attention is required for the most sensitive areas to desertification in order to achieve sustainable land use in such fragile agro-ecosystems.