The modulation of the electronic structure of metal oxides is crucial to enhance their gas‐sensing performance. However, there is lacking in profound study on the effect of electronic structure regulation on sensing performance. Herein, we propose an innovative strategy of Jahn–Teller distortion‐induced electronic configuration regulation of Co3O4 to improve acetone sensing performance. After the introduction of Mn3+ into Co3O4 (Mn‐Co3O4), the Jahn–Teller distortion of high‐spin Mn3+ (t2g3eg1) conversed to low‐spin Mn4+ (t2g3eg0), resulting in conversion of Co3+ (t2g6eg0) into Co2+ (t2g6eg1). As expected, Mn‐Co3O4 exhibits a high response value of 46.7 toward 100 ppm acetone, low limit of detection of 0.75 ppb, high selectivity, and high stability, which are overwhelmingly superior to previous Co3O4‐based acetone sensors. The dynamics and thermodynamics analysis demonstrate that the Mn doping improves sensing reaction rate, reduces reaction barrier, and promotes the charge transfer. The theoretical calculations further prove the charge transfer from Mn to Co derived from Jahn–Teller distortion and support promoting the adsorption of acetone on Co3O4 by Mn dopant. Moreover, we demonstrated the substantial potential application of Mn‐Co3O4 sensor as a monitoring gas sensor in pest resistance of Arabidopsis. This work provides a new strategy to design sensing materials from electronic configuration perspective.image