Separation of structurally similar components from their mixtures is one of the most promising applications of metal−organic frameworks (MOFs). A high efficiency of such molecular sieving requires fine tuning of the MOF structure. In this work, we investigate subtle metal-and temperature-induced changes in window dimensions of zeolitic imidazolate frameworks (ZIF-8(Zn) and ZIF-67(Co)) and apply such structural tuning for efficient separation of xylene isomers (p-, m-, and o-xylenes). The use of Co instead of Zn favorably modifies window geometry: it accelerates the diffusion of all components by a factor of 2−3 while maintaining closely the same separation efficiency as that of ZIF-8(Zn). Outstanding selectivity above 18:1 and faster isolation of demanded p-xylene from the ternary mixture using ZIF-67(Co) have been demonstrated at room temperature, opening new horizons for its energy-efficient xylene separation. More generally, our findings suggest the prospective ways to tune various MOFs for target liquidstate separations.