Interfacial polymerization technique has been widely employed to prepare reverse osmosis (RO) and nanofiltration (NF) membranes. The present study explores the possibility of preparing a polyamide membrane by interfacial polymerization and its utilization for the separation of CO2 and H2S from CH4. A novel ultraporous substrate of polysulfone (PSF) was prepared by phase inversion technique from a solution containing 18% PSF and 4% propionic acid in dimethyl formamide (DMF) solvent. Thin film composite (TFC) polyamide membrane was synthesized on PSF substrate from the reaction between meta-phenylene diamine in an aqueous media and isophthaloyl chloride in hexane. The membrane prepared was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) to study intermolecular interactions, crystallinity, thermal stability and surface morphology, respectively. Gas permeabilities of pure CO2, H2S, CH4, O-2, and N-2 gases were measured using the indigenously built permeation cell incorporated into a high-pressure gas separation manifold. At the feed pressure of 1 MPa, the membrane exhibited permeances of 15.2 GPU for CO2 and 51.6 GPU for H2S with selectivities of 14.4 and 49.1 for CO2/CH4 and H2S/CH4 systems, respectively. The observed N-2 permeance of 0.95 GPU was close to that of CH4. The corresponding O-2 permeance was 5.13 GPU with a reasonably high O-2/N-2 selectivity of 5.4. The effect of feed pressure on polyamide membrane performance was examined. Further, molecular dynamics (MD) simulations were employed to compute the cohesive energy density (CED), solubility parameter (delta) and sorption of CO2, H2S, CH4, O-2, and N-2 gases in polyamide membrane to corroborate theoretical study with experimentally determined gas transport properties.