The effect of the reinforcement spatial distribution on the mechanical behavior was investigated in model metal-matrix composites. Homogeneous microstructures were made up of a random dispersion of spheres. The inhomogeneous ones were idealized as an isotropic random dispersion of spherical regions—which represent the clusters—with the spherical reinforcements concentrated around the cluster center. The uniaxial tensile stress-strain curve was obtained by finite element analysis of three-dimensional multiparticle cubic unit cells, which stood as representative volume elements of each material, with periodic boundary conditions. The numerical simulations showed that the influence of reinforcement clustering on the macroscopic composite behavior was weak, but the average maximum principal stress in the spheres—and its standard deviation—were appreciably higher in the inhomogeneous materials than in the homogeneous ones (up to 12 and 60%, respectively). The fraction of broken spheres as a function of the applied strain were computed from experimental values of the Weibull parameters for the strength of the spheres, and the local stress computed in the simulations. It was found that the presence of clustering greatly increased (by a factor between 3 and 6) the fraction of broken spheres, leading to a major reduction of the composite flow stress and ductility.