Flea-borne typhus (FBT) is a febrile rickettsial disease caused by the bacteria Rickettsia typhi. In the United States, rats, opossums, and cats act as reservoir hosts of R. typhi and can readily transmit the bacteria to feeding flea vectors (Xenopsylla cheopis and Ctenocephalides felis). Formerly referred to as murine typhus, FBT was historically among the most common vector-borne diseases in the U.S. before nationwide public health practices effectively controlled FBT through pest control. In recent years, however, reported cases of FBT have risen in California, Texas, and Hawai’i. Understanding the current epidemiology of FBT is becoming ever more important to interpret and respond to the changing trends in FBT. This dissertation aimed to contribute to the body of knowledge regarding FBT epidemiology and ecology in California.In Chapter 1, we characterized FBT epidemiology in California from 2011 to 2019 by reviewing incidence, clinical course, and exposure histories collected in surveillance reports. Eight spatiotemporal clusters and areas with persistent FBT transmission were highlighted in Los Angeles County and Orange County using SatScan. Chapter 2 used a Bayesian hierarchical zero-inflated Poisson model with a spatially conditional autoregressive random effect to assess the relationship between population-level socioeconomic and built environment variables and FBT surveillance reporting. As measured by the Healthy Places Index, census tracts with greater socioeconomic advantage were associated with higher rates of FBT surveillance reporting (IRR = 1.34; 95% CI [1.07, 1.69]). Census tract demographics, economic variables, housing characteristics, and land use were also discussed. In Chapter 3, we constructed a novel mathematical transmission model of FBT using ordinary differential equations (ODEs) resembling the ecology of R. typhi in California. Sensitivity tests were performed using Latin hypercube sampling and partial rank correlation coefficients to identify parameters influential to human R. typhi infections. Sensitivity analyses highlighted human-opossum exposure and opossum-flea index as highly influential to the predicted proportion of humans infected in a population. Scenario analyses representing possible intervention activities were evaluated and discussed to demonstrate practical applications of the model. The results of these chapters characterize the recent epidemiology of FBT in California, provide context for public health FBT surveillance practices, and present a mathematical framework to model R. typhi transmission. Together, these will improve our understanding of FBT epidemiology and ecology and inform local-level public health intervention activities.