Listeriosis can cause human death via infection by Listeria monocytogenes (LMs) with a high fatality rate of 20–30 %. Detection of 3-hydroxy-2-butanone (3H-2B) biomarker of LMs can achieve estimation of LMs content, which is of great significance for human health. Exploring porous metal oxide semiconductors (MOSs) with rich vacancies towards 3H-2B sensing is quite promising for achieving this goal. Herein, we report a highly sensitive 3H-2B sensor based on novel 3D porous ZnO with rich oxygen vacancies which was facilely obtained by sacrificing Zn foam in oxalic acid and subsequent thermal decomposition. The ZnO sensor displays ultrahigh sensor response of Ra/Rg = 328@5 ppm, super-low detection limit of 0.001 ppm, excellent cycling stability and selectivity and good linear response at 120 °C, showing great potential for precise detection of 3H-2B biomarker. The porous structure and increased oxygen vacancies contribute greatly to the adsorption of active oxygen species therefore the sensing reactions on ZnO surface, which accounts for the high sensing performance. Our work provides an ingenious strategy to produce novel 3D ZnO with rich oxygen vacancies as well as new insights for boosting the detection of LMs.