We fabricated a highly robust and flexible gas diffusion barrier (GDB) with a multi-interfacial system. Our GDB film had a nanolaminate (NL) structure composed of 1-nm-thick ZnO, Al2O3, and MgO sublayers (ZAM). The ZAM NL single layer exhibits a water vapor transmission rate (WVTR) value of 1.92 × 10−5 g/m2/day. Furthermore, a WVTR value of 3.18 × 10-6 g/m2/day was achieved with a thickness of sub-500 nm by fabricating stacking structures of 2.5 dyads with organic layers. The multi-barrier demonstrated mechanical reliability with little WVTR change at a tensile strain of about 1%. The ZAM NL film helps to delay the occurrence of cracking and delamination in barrier films in comparison to previous single-layer films. Thus, a multi-interfacial and defect-decoupled ZAM NL structure was effectively designed considering the transmittance, gas diffusion barrier properties, and flexibility.