GSDMD promotes influenza virus-induced mortality through neutrophil amplification of inflammation. Influenza virus activates inflammasome pathways, which can be beneficial or harmful. This study investigates GSDMD, a pore-forming protein activated by inflammasomes, during influenza infection. GSDMD knockout (KO) mice show reduced weight loss, lung dysfunction, and mortality compared to wild-type (WT) mice, despite similar viral loads. Infected GSDMD KO mice have decreased inflammatory gene signatures, including reduced neutrophil activation. Directly infected neutrophils release DNA and tissue-damaging enzymes, which depend on GSDMD. Neutrophil depletion in WT mice reduces mortality, lung inflammation, and dysfunction, similar to GSDMD KO mice. These findings suggest GSDMD promotes lung neutrophil responses that amplify influenza-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic approach for severe influenza. Influenza A virus remains a global health threat, with severe infections characterized by excessive inflammation and tissue damage. The NLRP3 inflammasome is a key player in IAV infection, with both beneficial and pathological effects. While NLRP3 knockout mice show increased mortality, blocking the inflammasome is beneficial. GSDMD, cleaved by inflammasome-activated caspases, forms pores that release pro-inflammatory cytokines, but excessive pore formation leads to pyroptotic cell death. Despite its role in inflammation and pyroptosis, GSDMD's contribution to viral pathogenesis has been minimally studied. In vitro, GSDMD is not essential for macrophage death from influenza infection, but its role in viral pathogenesis remains unclear. This study explores GSDMD's function in IAV infections using GSDMD KO mice, which experience reduced lung inflammation, dysfunction, and mortality compared to WT mice. The absence of GSDMD does not affect virus loads or hinder recovery. GSDMD is identified as a potential target for reducing pathological neutrophil activities and influenza severity. GSDMD deficiency reduces inflammatory gene expression, including cytokines and chemokines, and neutrophil activation. Neutrophil depletion in WT mice recapitulates the protective effects of GSDMD deficiency. Neutrophils are activated in IAV infection, and their dysfunction in GSDMD KO mice suggests that GSDMD is essential for neutrophil function. Neutrophil depletion in WT mice reduces influenza severity, similar to GSDMD KO mice. These results indicate that neutrophils amplify inflammation and lung dysfunction during IAV infection. GSDMD is essential for neutrophil function during IAV infection, including DNA release and enzyme secretion. Neutrophil depletion in GSDMD KO mice does not provide additional protection, suggesting that neutrophils are the primary drivers of inflammation in IAV infectionGSDMD promotes influenza virus-induced mortality through neutrophil amplification of inflammation. Influenza virus activates inflammasome pathways, which can be beneficial or harmful. This study investigates GSDMD, a pore-forming protein activated by inflammasomes, during influenza infection. GSDMD knockout (KO) mice show reduced weight loss, lung dysfunction, and mortality compared to wild-type (WT) mice, despite similar viral loads. Infected GSDMD KO mice have decreased inflammatory gene signatures, including reduced neutrophil activation. Directly infected neutrophils release DNA and tissue-damaging enzymes, which depend on GSDMD. Neutrophil depletion in WT mice reduces mortality, lung inflammation, and dysfunction, similar to GSDMD KO mice. These findings suggest GSDMD promotes lung neutrophil responses that amplify influenza-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic approach for severe influenza. Influenza A virus remains a global health threat, with severe infections characterized by excessive inflammation and tissue damage. The NLRP3 inflammasome is a key player in IAV infection, with both beneficial and pathological effects. While NLRP3 knockout mice show increased mortality, blocking the inflammasome is beneficial. GSDMD, cleaved by inflammasome-activated caspases, forms pores that release pro-inflammatory cytokines, but excessive pore formation leads to pyroptotic cell death. Despite its role in inflammation and pyroptosis, GSDMD's contribution to viral pathogenesis has been minimally studied. In vitro, GSDMD is not essential for macrophage death from influenza infection, but its role in viral pathogenesis remains unclear. This study explores GSDMD's function in IAV infections using GSDMD KO mice, which experience reduced lung inflammation, dysfunction, and mortality compared to WT mice. The absence of GSDMD does not affect virus loads or hinder recovery. GSDMD is identified as a potential target for reducing pathological neutrophil activities and influenza severity. GSDMD deficiency reduces inflammatory gene expression, including cytokines and chemokines, and neutrophil activation. Neutrophil depletion in WT mice recapitulates the protective effects of GSDMD deficiency. Neutrophils are activated in IAV infection, and their dysfunction in GSDMD KO mice suggests that GSDMD is essential for neutrophil function. Neutrophil depletion in WT mice reduces influenza severity, similar to GSDMD KO mice. These results indicate that neutrophils amplify inflammation and lung dysfunction during IAV infection. GSDMD is essential for neutrophil function during IAV infection, including DNA release and enzyme secretion. Neutrophil depletion in GSDMD KO mice does not provide additional protection, suggesting that neutrophils are the primary drivers of inflammation in IAV infection