Abstract Multidrug‐resistant bacterial infections have become a global public health issue. To solve this dilemma, single‐atom nanozymes have been used as versatile antibiotics. However, the efficacy of individual nanozyme is hindered by their limited catalytic activity and antibacterial effect. Herein, a novel N 3 ‐Fe 1 ‐Mn 1 ‐N 2 S nanozyme (Fe/Mn‐SNC), with neighboring Mn and Fe dual single‐atom pairs decorated on yolk‐shell‐like carbon skeleton, is constructed through partial modulation of Fe‐Mn dual site coordination by sulfur atoms. The developed Fe/Mn‐SNC possesses superior multienzyme‐like cascade activities (oxidase‐, superoxide‐, and peroxidase‐like activities). It catalyzes the conversion of O 2 into O 2 ·− through its oxidase‐like activity, which is then decomposed into H 2 O 2 by its superoxide‐like enzyme properties. Ultimately, ·OH is generated under the influence of peroxidase‐like activity. This process effectively kills bacteria without the addition of H 2 O 2 , contributing to the overcoming of bacterial resistance issues. Density functional theory calculations indicate that the direct coordinated S atom enhances the oxidase‐like activity. The Fe‐Mn dual‐atomic site provides an additional active site for the enhancement of the superoxidase‐ and peroxidase‐like activities. The Fe/Mn‐SNC, with high antibacterial effect and biosafety, showing its wide potential applications in medical technology and consumer care. This work opens a new avenue for designing multifunctional single‐atom nanozymes for antibacterial applications.