Coccidioidomycosis (Valley fever) is an infection caused by the soil-dwelling fungus Coccidioides spp., which usually manifests as a mild self-limited respiratory illness or pneumonia but can result in severe disseminated disease and, rarely, death (1,2). In California, coccidioidomycosis incidence increased nearly 800% from 2000 (2.4 cases per 100,000 population) to 2018 (18.8) (2-4). The California Department of Public Health (CDPH) reports statewide and county-level coccidioidomycosis incidence annually; however, a comprehensive regional analysis has not been conducted. Using California coccidioidomycosis surveillance data during 2000-2018, age-adjusted incidence rates were calculated, and coccidioidomycosis epidemiology was described in six regions. During 2000-2018, a total of 65,438 coccidioidomycosis cases were reported in California; median statewide annual incidence was 7.9 per 100,000 population and varied by region from 1.1 in Northern and Eastern California to 90.6 in the Southern San Joaquin Valley, with the largest increase (15-fold) occurring in the Northern San Joaquin Valley. When analyzing demographic data, which was available for >99% of cases for sex and age and 59% of cases for race/ethnicity, median annual incidence was high among males (10.2) and Black persons (9.0) consistently across all regions; however, incidence varied among Hispanics and adults aged 40-59 years by region. Tracking these surveillance data at the regional level reinforced understanding of where and among what demographic groups coccidioidomycosis rates have been highest and revealed where rates are increasing most dramatically. The results of this analysis influenced the planning of a statewide coccidioidomycosis awareness campaign so that the messaging, including social media and TV and radio segments, focused not only on the general population in the areas with the highest rates, but also in areas where coccidioidomycosis is increasing at the fastest rates and with messaging targeted to groups at highest risk in those areas.