A rapid, sensitive, and eco-friendly micellar high-performance thin-layer chromatography (HPTLC) technique for the simultaneous analysis of cefoperazone and sulbactam in pure and vial pharmaceutical formulation was developed. Merck aluminum HPTLC plates covered with silica gel 60 F₂₅₄ were used as the stationary phase; acetone‒ethanol‒ethyl acetate‒2% sodium dodecyl sulfate‒glacial acetic acid (3:2:4:1:0.5, V/V) were used as the mobile phase. This chromatographic system results in symmetric, compact peaks at R_F values of (0.45 ± 0.015) and (0.69 ± 0.008) for cefoperazone and sulbactam, respectively. Densitometric scanning of the separated spots was done at 265 nm. The proposed method can quantitatively analyze cefoperazone and sulbactam in their laboratory prepared combinations and vials pharmaceutical formulation. The environmental greenness of the proposed HPTLC method was successfully assessed by the new green analytical procedure index. The method is considered to be a green eco-friendly HPTLC method because of its usage to green solvents, minimal waste production, and short time of analysis. The proposed method can also be helpful in the routine quality control analysis of the studied medications.