Neutrophil extrusion of neutrophil extracellular traps (NETs) and concomitant cell death (NETosis) provides host defense against extracellular pathogens, while macrophage death by pyroptosis enables defense against intracellular pathogens. Here we report the surprising discovery that GSDMD connects these cell death modalities. We show that neutrophil exposure to cytosolic lipopolysaccharide or cytosolic Gram-negative bacteria (Salmonella ΔsifA, C. rodentium) activates non-canonical (caspase-4/11) inflammasome signaling and triggers GSDMD-dependent neutrophil pyroptosis. Remarkably, GSDMD-dependent death induces neutrophils to extrude antimicrobial NETs. Caspase-11 and GSDMD are required for neutrophil plasma membrane rupture during the final stage of NET extrusion. Unexpectedly, caspase-11 and GSDMD are also required for early features of NETosis, including nuclear delobulation and DNA expansion; this is mediated by the coordinate actions of caspase-11 and GSDMD in mediating nuclear membrane permeabilization and histone degradation. In vivo application of DNase I to dissolve NETs during murine Salmonella ΔsifA challenge increases bacterial burden in wild-type but not Casp11-/-and Gsdmd-/-mice. We thus reveal that neutrophils deploy a novel inflammasome- and GSDMD-dependent NETosis mechanism against cytosolic intruders, to ensnare bacteria upon the NET and prevent cytosolic infection. The discovery of caspase-11-induced NET extrusion defines a new nuclear function for GSDMD, with broad relevance for cell death, as well as infectious, inflammatory and autoimmune diseases.