Image processing of multispectral data (Landsat-8 and ASTER) in combination with field studies and petrographic investigations was used for the lithologic mapping of the highly fractionated Humr Akarim (HA) granite pluton and the adjacent area in the Eastern Desert of Egypt. The image processing techniques applied include data transformation techniques such as band ratio, principal component analysis, and minimum noise fraction. Processing of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data is suitable for distinguishing the lithologic units of the HA granite pluton, which have similar mineralogy and chemical composition but differ in texture and microstructures. False Color Composite (FCC) image of the principal component based on standard deviation (PC4, PC2, and PC7 in RGB) is the most appropriate processing technique and effectively highlights significant geological features in HA granite pluton. In comparison to the HA granite pluton, analysis of Landsat images is more favorable and accurate in distinguishing the lithologic units, layering, and folding in the surrounding metavolcanoclastic rocks. Verification of the resulting geological map in the field shows high accuracy and reliability. The resulting geological map is more elaborated and detailed compared to previously published maps based only on field observations, petrographic studies, and chemical composition. It is suggests that the high-intensity lineaments zones detected on the Landsat 8 panchromatic band are zones of significant amounts of mineralization.