Background Increased IL-17A production has been associated with more severe asthma; however, the mechanisms whereby IL-17A can contribute to IL-13–driven pathology in asthmatic patients remain unclear. Objective We sought to gain mechanistic insight into how IL-17A can influence IL-13–driven responses. Methods The effect of IL-17A on IL-13–induced airway hyperresponsiveness, gene expression, mucus hypersecretion, and airway inflammation was assessed by using in vivo models of IL-13–induced lung pathology and in vitro culture of murine fibroblast cell lines and primary fibroblasts and human epithelial cell lines or primary human epithelial cells exposed to IL-13, IL-17A, or both. Results Compared with mice given intratracheal IL-13 alone, those exposed to IL-13 and IL-17A had augmented airway hyperresponsiveness, mucus production, airway inflammation, and IL-13–induced gene expression. In vitro , IL-17A enhanced IL-13–induced gene expression in asthma-relevant murine and human cells. In contrast to the exacerbating influence of IL-17A on IL-13–induced responses, coexposure to IL-13 inhibited IL-17A–driven antimicrobial gene expression in vivo and in vitro . Mechanistically, in both primary human and murine cells, the IL-17A–driven increase in IL-13–induced gene expression was associated with enhanced IL-13–driven signal transducer and activator of transcription 6 activation. Conclusions Our data suggest that IL-17A contributes to asthma pathophysiology by increasing the capacity of IL-13 to activate intracellular signaling pathways, such as signal transducer and activator of transcription 6. These data represent the first mechanistic explanation of how IL-17A can directly contribute to the pathogenesis of IL-13–driven pathology.