A diffuse and continuous monitoring of the in-service structural response of buildings can allow for the early identification of the formation of cracks and collapse mechanisms before the occurrence of severe consequences. In the case of existing masonry constructions, the implementation of tailored Structural Health Monitoring (SHM) systems appears quite significant, given their well-known susceptibility to brittle failures. Recently, a new sensing technology based on smart bricks, i.e., piezoresistive brick-like sensors, was proposed in the literature for the SHM of masonry constructions. Smart bricks can be integrated within masonry to monitor strain and detect cracks. At present, the effectiveness of smart bricks has been proven in different structural settings. This paper contributes to the research by investigating the strain-sensitivity of smart bricks of standard dimensions when inserted in masonry walls subjected to in-plane shear loading. Real-scale masonry walls instrumented with smart bricks and displacement sensors were tested under diagonal compression, and numerical simulations were conducted to interpret the experimental results. At peak condition, numerical models provided comparable strain values to those of smart bricks, i.e., approximately equal to 10−4, with similar trends. Overall, the effectiveness of smart bricks in strain monitoring and crack detection is demonstrated.