Single crystals of two pyridine isomers containing cyano and thiophene moieties {systematic names: (Z)-2-(pyridine-2-yl)-3-(thiophen-2-yl)acrylonitrile, C₁₂H₈N₂S, I and (Z)-2-(pyridine-3-yl)-3-(thiophen-2-yl)acrylonitrile, C₁₂H₈N₂S, II} were obtained from ethanol-cyclohexane mixture. The thiophene ring wasfound to be disordered over two orientations (syn and anti) in II. The potential energy surface scan of thiophene ring rotation suggests that the syn conformer is more stable by ≈4 kcal mol−1 than that of the anti-conformer. The optimized structures obtained using the DFTmethod (M06-2X/cc-pVTZ level of theory) showa high degree of similarity with the experimental structures. A detailed experimental and theoretical analysis on the intra- and intermolecular interactions observed in these structures is reported. The molecules arranged in the crystalline state are completely different in I and II. Intermolecular interactions are qualitatively analyzed using Hirshfeld surface and its associated 2D fingerprint plots. The intermolecular interaction energies of different molecular pairs are calculated using the PIXEL method. Several weak non-covalent interactions such as C–H · · ·N, C–H · · ·π, C–H · · ·S, π· · ·π and S · · · N contacts play a vital role in the stabilization of crystal structures. These interactions are further explored by the topological analysis of the electron density based on the quantum theory of the atoms-in-molecules approach.