The separation of phenylenediamine (PDA) isomers is crucial in the field of chemical manufacturing. Herein, we presented a strategy for the separation of PDA isomers (para-phenylenediamine, p-PDA; meta-phenylenediamine, m-PDA; ortho-phenylenediamine, o-PDA) using four supramolecular framework materials of ns-cucurbit[10]uril (ns-Q[10]), (1) ns-Q[10](Cd), (2) ns-Q[10](Mn), (3) ns-Q[10](Cu), (4) ns-Q[10](Pb). Our findings indicated that these supramolecular framework materials of ns-Q[10] showed remarkable selectivity for para-phenylenediamine (p-PDA) in p-PDA, m-PDA, and o-PDA mixtures, respectively. The variations in selectivity observed in these four single-crystal structures arose from variations in the thermodynamic stabilities and binding modes of the host-guest complexes. Importantly, the supramolecular framework based on ns-Q[10] exhibited selective accommodation of p-PDA over its isomers. This study highlighted the practical application of ns-Q[10] in effectively separating PDA isomers and demonstrated the potential utility of ns-Q[10] in isolating other organic molecules.