The infection is caused by breathing in the spores of a fungus found in desert regions such as Arizona or California's San Joaquin Valley. The disease can have an acute, chronic, or disseminated form.

The chronic form usually develops after a latent period of months to years following an initial benign infection which may go undiagnosed. Lung abscesses may form and may rupture into the pleural spaces causing empyema (pus in the pleural space) or bronchopleural fistula. Scarring (fibrosis) and cavities may gradually form in the upper lungs as the chronic form of coccidioidomycosis slowly progresses over months to years.

Still, the majority of pulmonary coccidioidomycosis infections do not become chronic. In fact, the majority of infections cause no symptoms and are only recognized by a positive coccidioidin skin test.

Dark skinned people and people with a weak immune system are more susceptible to infection and more likely to form chronic or disseminated (spreading to other organs) forms of the disease.