Background: In Cambodia, malaria persists with changing epidemiology and resistance to antimalarials. This study aimed to describe how malaria has evolved spatially from 2006 to 2019 in Cambodia. Methods: We undertook a secondary analysis of existing malaria data from all government healthcare facilities in Cambodia. The epidemiology of malaria was described by sex, age, seasonality, and species. Spatial clusters at the district level were identified with a Poisson model. Results: Overall, incidence decreased from 7.4 cases/1000 population in 2006 to 1.9 in 2019. The decrease has been drastic for females, from 6.7 to 0.6/1000. Adults aged 15–49 years had the highest malaria incidence among all age groups. The proportion of Plasmodium (P.) falciparum + Mixed among confirmed cases declined from 87.9% (n = 67,489) in 2006 to 16.6% (n = 5290) in 2019. Clusters of P. falciparum + Mixed and P. vivax + Mixed were detected in forested provinces along all national borders. Conclusions: There has been a noted decrease in P. falciparum cases in 2019, suggesting that an intensification plan should be maintained. A decline in P. vivax cases was also noted, although less pronounced. Interventions aimed at preventing new infections of P. vivax and relapses should be prioritized. All detected malaria cases should be captured by the national surveillance system to avoid misleading trends.