This study focuses on a historical leather cover of a manuscript dating back to the 10th A.H century from Al-Azhar Library. The study aims to use analytical techniques to identify the components of the historical leather cover of the manuscript, and to explain its deterioration process. Analytical methods used in this study were visual assessment, investigation of the surface morphology by a digital microscope and a scanning electron microscope (SEM), Attenuated total reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), amino acid analysis, identification of fungi, and measurement of pH. The results revealed that the leather suffered from brittleness, white stain, dust, fungal stains, cracks, in addition to missing and burnt parts. The results of SEM revealed that goatskin was identified as the animal skin of the historical leather cover of the manuscript. ATR-FTIR analysis revealed the degradation of chemical composition of the historical leather cover of the manuscript. The amino acid analysis stated that the chemical composition of historical cover of the manuscript suffered from deterioration through oxidation and hydrolysis mechanisms. Aspergillus sp < /em>, Chaetomium sp < /em>, Penicillium sp < /em>, and Fusarium sp < /em> were the most dominant fungi found. All analytical techniques used in this study proved that the historical leather cover of the manuscript is in urgent need of conservation.