Acetone exhibits flammability, explosiveness, and toxicity, rendering it a multifaceted hazard. Moreover, acetone serves as a vital biomarker for diabetes. Consequently, the demand for low-concentration acetone gas detection sensors is increasingly pressing in numerous sectors, including industrial processes and medical applications. In this study, we report a novel sensor based on Co3O4/ZnO nanorods and investigate the influence of Co doping-induced oxygen vacancies and the presence of Co3O4 on the sensing properties. The sensor was prepared through a simple one-step hydrothermal method and named Co/ZnONRs. The morphology, composition, and oxygen vacancy defects of the Co/ZnONRs were characterized using various techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and electron paramagnetic resonance (EPR). Characterization and gas sensing test results have demonstrated that the 1-Co/ZnONRs sensor outperformed previously reported designs, exhibiting high response values, short response times, good selectivity, and low detection limits toward acetone. Specifically, at 250 °C, the sensor demonstrated a response value of 833.33 toward 100-ppm acetone, which is an increase of ten times compared to the response value of ZnONRs, while the optimal operating temperature decreased by 50 °C, and the detection limit was as low as 100 ppb. The improved sensor performance is attributed to several factors such as changes in resistance caused by active sites generated by Co doping ZnO to form oxygen vacancies, the Co3O4/ZnO heterojunction, the high specific surface area of Co/ZnONRs, and the unique catalytic activity of Co3O4. These findings demonstrate the potential of our innovative design to significantly improve the accuracy and efficiency of gas sensors used in industrial processes and medical diagnoses.