Combining the chemical-specific adsorption properties of metal-organic framework (MOF) materials with the dielectric sensitivity of a novel open-ended hollow coaxial cable resonator (OE-HCCR), a mechanically-robust and portable gas sensor device (OE-HCCR-MOF) with high chemical selectivity and sensitivity is proposed and experimentally demonstrated. The operating principle of the device is based on changes in the dielectric property of the host MOF layer in response to variations in the types and concentrations of guest molecules. The changes in the dielectric property of the MOF layer modify the phase-matching condition of the microwave resonator, causing shifts in the resonance frequency of the device. By monitoring the resonance frequency shift, the adsorptions of guest molecules can be monitored in real-time and accurately quantified. In proof-of-concept demonstrations, a 200-μm layer of MOF (HKUST-1) was placed within an OE-HCCR to develop a prototype OE-HCCR-MOF sensor. The novel sensor showed high sensitivity to variations in the concentrations of carbon dioxide with good reversibility. The chemical selectivity of the prototype sensor for carbon dioxide compared to methane was also investigated.