This paper presents an innovative modelling approach for assessing the in-plane behaviour of masonry walls characterized by periodic arrangements of units and mortar joints. The proposed model is a typical d-FEM (Discontinuum Finite Element Model) consisting of deformable macro-blocks covering more than a single unit of masonry and separated by a reduced number of interface elements, which are properly arranged along pre-established potential crack/slip surfaces. To account for the modelling simplifications deriving from the proposed multi-unit discretization (MUDis), three of the mechanical parameters describing the adopted interface model, i.e. the Composite Interface (CI) model formulated by Lourenço & Rots, are optimised through an Evolutionary Polynomial Regression (EPR) technique relying on a Multi-Objective Genetic Algorithm (MOGA).In the first part of the paper, benchmark experimental tests taken from literature are reproduced to calibrate conventional CI-based FEM models and to generate therefrom a wide stock of masonry panels. Afterwards, the novel MUDis approach is applied to the generated wall population in order to evaluate its capability of replicating the in-plane response of a considerable number of masonry walls regardless of their geometrical and mechanical features. Extensive details on how deriving the optimal parameters of the CI model to allow for the reduction of interface elements inherent to the MUDis approach are provided, followed by a sensitivity analysis to evaluate the mesh dependency of the results.Finally, the proposed MUDis procedure is cross validated against the experimental results of the initial benchmark tests, allowing to demonstrate its computationally efficiency with respect to conventional micro-modelling procedures.