The cause of GPA is not yet known. Some research suggests that GPA may be triggered by exposure to silica or to infection with staphylococcus aureus bacteria though this is not proven.

The ANCA antibodies found in most patients with GPA play a role in causing the inflammation of the blood vessels by activating some types of white blood cell. The ANCA antibodies attach to the neutrophils in the blood causing activation. This makes the neutrophil attach to the blood vessel wall and cause damage by release of the chemicals that it usually uses to fight infection. It is not understood why patients develop ANCA antibodies.