Ozone is a common environmental air pollutant leading to respiratory illness. The mechanisms regulating ozone-induced airway inflammation remain poorly understood. We hypothesize that ozone-triggered inflammasome activation and interleukin (IL)-1 production regulate neutrophilic airway inflammation through IL-17A. Pulmonary neutrophilic inflammation was induced by extended (72 h) low-dose (0.7 ppm) exposure to ozone. IL-1 receptor 1 (Il1r1)(-/-), Il17 alpha(-/-) mice and the caspase-1 inhibitor acetyl-YVAD-chloromethylketone (Ac-YVAD-cmk) were used for in vivo studies. Cellular inflammation and protein levels in bronchial alveolar lavage fluid (BALF), cytokines, and IL-17A-producing gamma delta T-cells, as well as mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) release, and inflammasome activation in lung macrophages were analyzed. Ozone-induced neutrophilic airway inflammation, accompanied an increased production of IL-1 beta, IL-18, IL-17A, Granulocyte-colony stimulating factor (G-CSF), Interferon-gamma inducible protein 10 (IP-10) and BALF protein in the lung. Ozone-induced IL-17A production was predominantly in.dT-cells, and Il17 alpha-knockout mice exhibited reduced airway inflammation. Lung macrophages from ozone-exposed mice exhibited higher levels of mitochondrial ROS, enhanced cytosolic mtDNA, increased caspase-1 activation, and higher production of IL-1 beta. Il1r1-knockout mice or treatment with Ac-YVAD-cmk decreased the IL-17A production and subsequent airway inflammation. Taken together, we demonstrate that ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade.