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Canonical Wnt signaling plays a major role in regulating microbial pathogenesis. However, to date, its involvement in <i>A. hydrophila</i> infection is not well known. Using zebrafish (<i>Danio rerio</i>) kidney macrophages (ZKM), we report that <i>A. hydrophila</i> infection upregulates <i>wnt2</i>, <i>wnt3a</i>, <i>fzd5</i>, <i>lrp6,</i> and β-catenin (<i>ctnnb1</i>) expression, coinciding with the decreased expression of <i>gsk3b</i> and <i>axin</i>. Additionally, increased nuclear β-catenin protein accumulation was observed in infected ZKM, thereby suggesting the activation of canonical Wnt signaling in <i>A. hydrophila</i> infection. Our studies with the β-catenin specific inhibitor JW67 demonstrated β-catenin to be pro-apoptotic, which initiates the apoptosis of <i>A. hydrophila</i>-infected ZKM. β-catenin induces NADPH oxidase (NOX)-mediated ROS production, which orchestrates sustained mitochondrial ROS (mtROS) generation in the infected ZKM. Elevated mtROS favors the dissipation of the mitochondrial membrane potential (ΔΨ_m) and downstream Drp1-mediated mitochondrial fission, leading to cytochrome <i>c</i> release. We also report that β-catenin-induced mitochondrial fission is an upstream regulator of the caspase-1/IL-1β signalosome, which triggers the caspase-3 mediated apoptosis of the ZKM as well as <i>A. hydrophila</i> clearance. This is the first study suggesting a host-centric role of canonical Wnt signaling pathway in <i>A. hydrophila</i> pathogenesis wherein β-catenin plays a primal role in activating the mitochondrial fission machinery, which actively promotes ZKM apoptosis and helps in containing the bacteria.