Environmental and health monitoring requires low-cost, high-performance diethylamine (DEA) sensors. Materials based on metal-organic frameworks (MOFs) can detect hazardous gases due to their large specific surface area, many metal sites, unsaturated sites, functional connectivity, and easy calcination to remove the scaffold. However, developing facile materials with high sensitivity and selectivity in harsh environments for accurate DEA detection at a low detection limit (LOD) at room temperature (RT) is challenging. In this study, p-type semiconducting porous CuO x sensing materials were synthesized using a simple solvothermal process and annealed in an argon atmosphere at three different temperatures ( x = 400, 600, and 800 °C). Significant variations in particle size, specific area, crystallite size, and shape were noticed when the annealing temperature was elevated. Cu-MIL-53 annealed at 400 °C (CuO-400) has a typical nanoellipsoid (NEs) shape with a length of 61.5 nm and a diameter of 33.2 nm. Surprisingly, CuO-400 NEs showed an excellent response to DEA with an ultra-LOD ( R g / R a = 7.3 @ 100 ppb, 55% relative humidity), excellent selectivity and sensitivity ( R g / R a = 236 @ 15 ppm), exceptional long-term stability and repeatability, and a fast response/recovery period at RT, outperforming most previously reported materials. CuO-400 NEs have outstanding gas-sensing characteristics due to their high porosity, 1D nanostructure, unsaturated Cu sites (Cu + and Cu 2+ ), large specific surface area, and numerous oxygen vacancies. This study presents a generic approach to produce future CuO derived from Cu-MOFs-sensitive materials, revealing new insights into the design of effective sensors for environmental monitoring at RT.