Bruton’s tyrosine kinase (BTK) is essential for B cell functions. Its role in myeloid cells is less understood. More insights into its significance in myeloid cells are required to evaluate its potential as therapeutic target in the effector phase of antibody-induced autoimmune diseases when inhibiting the production of autoantibodies can suppress tissue inflammation only time delayed. Such situation can be found, e.g., in acute flares of pemphigoid diseases, a group of autoimmune blistering skin diseases. We examined the effect of neutrophil-specific Btk gene deficiency and of the BTK inhibitor ibrutinib on disease in the antibody-transfer model of bullous pemphigoid (BP)-like epidermolysis bullosa acquisita (EBA), a model solely reflecting the effector phase. We additionally investigated the effect of BTK inhibitors on responses of neutrophils relevant for autoimmune diseases in vitro. Both neutrophil-specific genetic deficiency of Btk and ibrutinib vastly protected from skin inflammation. Stimulation of murine neutrophils with immune complexes activated BTK and induced the release of leukotriene B4 (LTB4) and reactive oxygen species (ROS). Deficiency in Btk nullified LTB4 but not ROS release indicating differences in the cell signaling cascades regulating the release of LTB4 and ROS upon Fcγ receptor activation signaling. Collectively, our results indicate that skin inflammation in EBA is critically controlled by a Fcγ receptor – BTK – LTB4 axis in neutrophils. This highlights BTK as promising drug target to treat EBA and potentially other antibody-induced autoimmune disease.