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Aims: West Nile Virus (WNV) has remained a persistent source of vector‐borne disease risk in California since first being identified in the state in 2003. The geographic distribution of WNV activity is relatively widespread, but varies considerably across different regions within the state. Spatial variation in human WNV infection depends upon social‐ecological factors that influence mosquito populations and virus transmission dynamics. Measuring changes in spatial patterns over time is necessary for uncovering the underlying regional drivers of disease risk. Methods and Results: In this study, we utilized statewide surveillance data to quantify temporal changes and spatial patterns of WNV activity in California. We obtained annual WNV mosquito surveillance data from 2004 through 2021 from the California Arbovirus Surveillance Program. Geographic coordinates for mosquito pools were analysed using a suite of spatial statistics to identify and classify patterns in WNV activity over time. Conclusions: We detected clear patterns of non‐random WNV risk during the study period, including emerging hot spots in the Central Valley and non‐random periods of oscillating WNV risk in Southern and Northern California subregions. Our findings offer new insights into 18 years of spatio‐temporal variation in WNV activity across California, which may be used for targeted surveillance efforts and public health interventions. [ABSTRACT FROM AUTHOR]