A microfluidic-based gas sensor was chosen as an alternative method to gas chromatography and mass spectroscopy systems because of its small size, high accuracy, low cost, etc. Generally, there are some parameters, such as microchannel geometry, that affect the gas response and selectivity of the microfluidic-based gas sensors. In this study, we simulated and compared 3D numerical models in both simple and serpentine forms using COMSOL Multiphysics 5.6 to investigate the effects of microchannel geometry on the performance of microfluidic-based gas sensors using multiphysics modeling of diffusion, surface adsorption/desorption and surface reactions. These investigations showed the simple channel has about 50% more response but less selectivity than the serpentine channel. In addition, we showed that increasing the length of the channel and decreasing its height improves the selectivity of the microfluidic-based gas sensor. According to the simulated models, a serpentine microchannel with the dimensions W = 3 mm, H = 80 µm and L = 22.5 mm is the optimal geometry with high selectivity and gas response. Further, for fabrication feasibility, a polydimethylsiloxane serpentine microfluidic channel was fabricated by a 3D printing mold and tested according to the simulation results