This article presents the experimental results of a research on six manuscripts (three of the XVIII century and three of XIX century) belonging collection of old religious books to the Moldovan Metropolitan Church of Romania. Non-invasive techniques (optical microscopy [OM], scanning electron microscopy/energy dispersive X-ray system, X-ray fluorescence analysis, shrinkage temperature, and Fourier transform infrared spectroscopy/attentuated total reflectance) provided information on the degree of degradation and identification of the leather bookbinding type. Moreover, visual assessment and OM revealed the extent of the surface degradation (wane, biological attack, change color, etc.). The degradation extent of the skin bindings was determined on the 12 samples. The insight on the mechanism of degradation was accomplished by analyzing the deterioration of collagen fibers in terms of shrinkage temperature and chemical modifications induced by oxidative and hydrolytic processes. Shrinkage temperature values were lower compared with the literature data for collagen, indicating that the leather bookbinding suffered intrinsic damage. Morphological analysis was accomplished by microscopy and allowed the identification of skin type and provided information about its processing technique. Mineral elements were identified for leather composition and contributed to the information regarding the origin and the extent of degradation of the leather bookbinding, of the studied manuscripts. The analyzed results were useful in determining the state of preservation and were able to provide an increased efficiency of further restoration. The correlation of the obtained data brought new contributions to the knowledge of the leather covers for the book technique in the XVIII and XIX centuries in monastic workshops of Eastern Europe.