Indirect monitoring of Listeria monocytogenes (LM) via a gas sensor that can detect the bacterial metabolite 3-hydroxy-2-butanone (3H-2B) is a newly emerged strategy. However, such sensors are required simultaneously endow with outstanding selectivity, high sensitivity, and ppb-level detection limit, which remains technologically challenging. Herein, we have developed highly selective and sensitive 3H-2B sensors that consist of zinc oxide nanorods decorated with cobaltosic oxide nanoparticles (ZnO NRs/Co3O4 NPs), which have been synthesized by combined optimized hydrothermal and annealing process. Specifically, the ZnO NRs/Co3O4 NPs exhibit ultrahigh sensitivity to 5 ppm 3H-2B (Ra/Rg = 550 at 260 °C). The sensor prototypes enable detection as low as 10 ppb 3H-2B, show excellent long-term stability, and present remarkable selectivity through interfering selectivity survey and principal component analysis (PCA). Such outstanding sensing performance is attributed to the modulated electron depletion layer by n-p heterojunctions and abundant gas diffusion pathways via the radial architecture, which was verified via electrochemical impedance spectroscopy test, Mott-Schottky measurement, and ultraviolet-visible absorption analysis. Our highly selective and sensitive ZnO NRs/Co3O4 NPs have the potential in the real-time detection of 3H-2B biomarker.