Acetylacetone is a typical volatile organic compound (VOC), and long-term exposure to low concentrations or short-term exposure to high concentrations may cause adverse effects on the human respiratory and central nervous systems. Therefore, the development of efficient and reliable acetylacetone monitoring technologies is of great importance for environmental monitoring and industrial safety. In this work, a series of reduced graphene oxide-modified CuO composites with different rGO concentrations were successfully synthesized via a facile hydrothermal method, and their gas-sensing performances toward acetylacetone were systematically investigated. The results demonstrate that the composite prepared with an rGO concentration of 0.3 g/L, denoted as 0.3rGO/CuO, exhibits the most outstanding sensing properties among all samples. At the optimal operating temperature of 160 °C, the corresponding sensor delivers a high response value of 132.38 toward 100 ppm acetylacetone, representing an enhancement of approximately 369.4% compared with pristine CuO. The response and recovery times are approximately 47 s and 34 s, respectively. In addition, the sensor shows good selectivity against common interfering gases, as well as satisfactory repeatability and long-term stability, indicating its potential for practical acetylacetone detection. To gain deeper insight into the sensing enhancement mechanism, the structural, morphological, optical, and surface chemical properties of the rGO/CuO composites were comprehensively characterized. The incorporation of rGO is found to regulate the electronic structure and surface chemistry of CuO, leading to a narrowed optical band gap, enhanced interfacial charge transfer, and increased relative proportions of oxygen-vacancy-related and adsorbed-oxygen components. These changes can provide more active sites for gas adsorption and promote the surface redox reaction between adsorbed oxygen ions and acetylacetone molecules. Moreover, the conductive rGO network facilitates carrier transport and modulates the interfacial charge distribution between rGO and CuO, thereby amplifying the resistance variation during the sensing process. The synergistic effect of oxygen vacancy regulation, interfacial charge transfer, and conductive network construction ultimately contributes to the remarkable improvement in sensing response and response speed. This study provides an experimental basis for the rational design of rGO/CuO-based gas sensors for low-temperature acetylacetone detection and may offer guidance for developing high-performance VOC sensing materials.