The Nile River Basin (NRB) within East-Northern Africa is experiencing progressive aridity due to climate variability and changes in land use/land cover (LUC). To address these challenges, it is crucial to understand the interactions between LUC patterns and aridification at a basin broader scale. This study aims to assess the LUC shifts and aridity index changes under climate variability from 2000 to 2020. The LUC changes were evaluated using the land use dynamic index (K), and aridity index was calculated based on the UNEP classification. The results indicated essential patterns in the LUC classes, aridity index trends, and aridity index-based climate classes. The LUC dynamics in the basin showed a slow and progressive lateral change. The settlement area showed a significant increase of 3536.11 km2 with a K value of 9.71 %. The largest LUC decline was observed in the shrubland by 35,448 km2 with a K value of -0.31 % during the two decades. The overall aridity index slope decreased at an average rate of -4.5 x 103 per year. The forest LUC showed the most significant decrease in the aridity trends followed by shrubland and wetland LUC types, while the bare land experienced an increasing aridity trend. The aridity index in the arid, semi-arid, and hyper-arid lands increased by about 13.77 %. On the contrary, the aridity index in the dry, sub-humid, humid, and hyper-humid lands declined by -20.32 % during the study period. The outcome of this study can potentially serve as a basis for developing sustainable adaptation strategies in NRB, and the information can be further utilized in other climatic regions for comparative analyses.