A laboratory procedure aimed at generating a progressive deterioration of the interface between brick and mortar layers in controlled experimental conditions was developed at the Non Destructive Testing Laboratory of the Politecnico di Torino. It is intended as a preliminary stage in the design of a pre-qualification procedure to be applied to repair mortars for restoration of historical masonry buildings. Indeed, assessing the durability of repair products is a major concern because of the potential occurrence of de-bonding phenomena due to insufficient compatibility between original and repair materials, in terms of their mechanical characteristics. Therefore, the study of the long-term mechanical interaction between repair mortars and historical masonry substrate turns out to be crucial for the design of durable repair works. In this direction the evolutionary phenomenon of mortar de-bonding generated in the lab is analyzed here through the cohesive crack model. The numerical simulation of the laboratory tests was shown to be able to describe the experimental evidence correctly, thus allowing us to characterize the mechanical behavior of the interface. It is therefore possible to use the analysis presented here to predict de-bonding phenomena in problems with different boundary conditions by changing the simulation parameters properly.