<p>Cellular metamaterials manufactured from brittle solids are excellent candidates for thermal protection, filtration, and energy storage applications. Although their mechanical integrity is critical for their functionality, the failure mechanics of these materials and their connection to the macroscopic loading conditions are not yet fully understood. Here, we integrate additive manufacturing, micro-computed tomography, multiscale experiments, and high-fidelity computational modeling to predict the strength of brittle lattices under tensile and compressive loads. Our results show that tension-compression asymmetry in the strength of metamaterials arises from the interaction between topology, the flexural and tensile strength of the parent solid, and stress concentrations. By coupling material characterization at the strut level with high-fidelity modeling, our framework offers a systematic approach to elucidate the failure mechanism of brittle metamaterials with different topologies and predict the associated critical stresses under varying macroscopic loading conditions.</p>