Typhoid fever is a human host-restricted systemic infection caused by ingestion of fecally-contaminated food or water bearing Salmonella enterica serovar Typhi (S. Typhi). For decades, the Pacific Island nation of Samoa (population ~200,000) has faced unexplained, persistently endemic typhoid fever, despite improvements in water quality, sanitation, and economic development. Herein, epidemiologic analysis of surveillance data from 2008-2019 revealed that 53-193 blood culture-confirmed typhoid fever cases occurred annually in Samoa without seasonality. The greatest annual burden (number of cases/year) and incidence (cases/100,000 persons/year) occurred in primarily urban and peri-urban regions, where piped treated water reaches most households. Phylogenetic analyses of whole genome sequences (WGS) of 306 S. Typhi isolates from Samoa collected between 1983-2020 identified a dominant population of rare, Samoa-exclusive genotypes 3.5.3 and 3.5.4, which could be further divided into local sub-lineages. These Samoan genotypes are calculated to have most likely emerged in the 1970s with a shared common ancestry with other parent clade 3.5 isolates from South America, Southeast Asia, and Oceania. Furthermore, Samoan S. Typhi were reported susceptible to all clinically-relevant antibiotics, including those that are no longer effective in many other typhoid-endemic regions; indeed, resistance-conferring polymorphisms or genes were detected in <5% of isolates spanning decades of endemicity and despite suboptimal antibiotic prescribing practices. Finally, to elucidate patterns of transmission, point pattern spatial statistics and the high-resolution discerning power of WGS were integrated with detailed epidemiological data generated through household investigations of typhoid cases. Patterns identified were consistent with exposure within households in rural regions, dispersion of infections among a wider geographic area in urban regions, and transmission of genetically similar isolates among cases and asymptomatic shedders (carriers) identified through the household investigations. Notably, cases peaked during a period of increased population movement and dramatically decreased during two national lockdowns, indicating possible roles for population mobility and interaction in propagating typhoid fever. Together, these studies characterize the epidemiology and genomics of S. Typhi in Samoa, an endemic island setting in an understudied global region, and can directly assist the Samoa Ministry of Health and other similarly resourced Pacific Island public health programs in their typhoid control efforts.