Half-metals are always accompanied by ferromagnetism with undesired stray magnetic field which may be harmful in highly integrated circuits. By contrast, half-metallic antiferromagnets (HMAFMs) can achieve fully spin-polarized current without stray magnetic field, enabling spintronic filed sensing and magnetic memories. Using first-principles calculations, we demonstrated that the tantalizing HMAFM can be realized in a two-dimensional (2D) metal–organic framework (MOF) containing Co ions and octa-amino-substituted iron-porphyrazines (CoFePz). The strong p–d exchange interaction between ions and ligands leads to an antiferromagnetic ground state with metallic features in one spin direction and semiconducting features in the opposite spin direction. Monte Carlo simulations based on the Ising model on an edge-centered square lattice indicate that the Néel temperature of the CoFePz (247 K) is much higher than the temperature of liquid nitrogen. Considering the huge number of MOFs, it is expected that the present findings can shed light on a new way to develop organic HMAFMs.