SL ligand (E)‐2‐(((2‐(tert‐butylthio) phenyl) imino)methyl)‐4‐chlorophenol) and its Cu(II) complex Cu(C14H12ClNOS)2 are synthesized and characterized by FTIR, SEM, EDX and TGA. Single crystal X‐ray diffraction studies revealed that the ligand and Cu(II) complex crystallizes in identical space group and the copper complex exhibits square planar geometry (τ4=0). SL and copper complex show C−Cl⋯π and C−H⋯π interaction respectively enables the formation of multi‐dimensional supramolecular architecture and its nature of interactions is quantified by Hirshfeld surface analysis. The strength of the interaction and 3D topology of crystal packing are visualized through an energy framework. Further, the physical nature of intramolecular interactions is assessed by QTAIM and NCI index model. DFT was employed to evaluate the optimized electronic structure, HOMO‐LUMO, energy gap, molecular properties and global parameters. The copper complex exhibited good antibacterial activity against the S.aureus and MRSA and compared with the standard drug (gentamicin). The molecular docking studies of the copper complex show a high affinity towards penicillin‐binding protein 2 and topoisomerase II DNA gyrase. trans N−O Cu(II) complex is compared with symmetric compartmental ligand and structurally characterized by single‐crystal X‐ray diffraction. The energetic difference of non‐covalent interactions are assed by quantum computational studies.