Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification due to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture, and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here, we disclose a porous, robust homochiral metal–organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural l-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale.