Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Macrophages use a compartmentalized dual detection system to respond to bacterial infection, with Toll-like receptors (TLRs) detecting extracellular or vacuolar stimuli and Nod-like receptors (NLRs) detecting cytosolic perturbations. While wild-type *Salmonella typhimurium* infection is lethal to mice, a strain that persistently expresses flagellin was cleared by the cytosolic flagellin detection pathway via NLRC4 activation of caspase-1. This clearance was independent of IL-1β and IL-18, but was associated with caspase-1-induced pyroptotic cell death, which released bacteria from macrophages and exposed them to reactive oxygen species in neutrophils for killing. Similarly, caspase-1 cleared *Legionella* and *Burkholderia* without cytokine-dependent mechanisms. This study demonstrates that caspase-1 clears intracellular bacteria *in vivo* independently of IL-1β and IL-18, establishing pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Macrophages use a compartmentalized dual detection system to respond to bacterial infection, with Toll-like receptors (TLRs) detecting extracellular or vacuolar stimuli and Nod-like receptors (NLRs) detecting cytosolic perturbations. While wild-type *Salmonella typhimurium* infection is lethal to mice, a strain that persistently expresses flagellin was cleared by the cytosolic flagellin detection pathway via NLRC4 activation of caspase-1. This clearance was independent of IL-1β and IL-18, but was associated with caspase-1-induced pyroptotic cell death, which released bacteria from macrophages and exposed them to reactive oxygen species in neutrophils for killing. Similarly, caspase-1 cleared *Legionella* and *Burkholderia* without cytokine-dependent mechanisms. This study demonstrates that caspase-1 clears intracellular bacteria *in vivo* independently of IL-1β and IL-18, establishing pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.