The preparation of highly ordered porous semiconducting metal oxides (SMOs) films is a hot issue in the field of chemical sensor. Herein, we successfully fabricated 3D inverse opal (IO) ZnO-In₂O₃composites multilayer films (MFs) via a novel strategy that combing ultrasonic nebulization deposition technique with polystyrene (PS) spheres template. Such one-step synthetic method is advantageous to achieve the construction of large-scale interconnected macro-porous (pore size: similar to 170 nm) structure in composites materials, which is beneficial for facilitating gas molecule transport into the sensing layers and accelerating the surface reactions process. More significantly, by using this method, the large-scale 3D IO MFs made in this work can be easily transferred onto any target substrates without being destroyed. Due to the IO multilayer films structure and abundant hetero-interfaces, the 3D IO ZnO-In₂O₃MFs-based gas sensor exhibited higher response toward acetone at lower operating temperature, better selectivity and long-term stability, faster recovery speed and lower detection limit. Consequently, the approach described herein is more suitable for the synthesis of porous composites materials films, in order to fabricate high performance chemical sensor.