Bacterial regional demonstration after global dissemination is an essential pathway for selecting distinct finesses. However, the stepwise evolution of the resistome during the transition to endemicity remains unaddressed. Using the most comprehensive whole-genome sequencing dataset ofSalmonellaenterica serovar Gallinarum (S. Gallinarum) collected from 16 countries over the past century, we first elucidated the pathogen's population structure. Subsequently, we revealed the international transmission and evolutionary history ofS. Gallinarum to recent endemicity through phylogenetic analysis conducted within a spatiotemporal Bayesian framework. Our findings indicate that the independent acquisition of the resistome via the mobilome, primarily through plasmids, transposons, and prophages, shapes a unique antimicrobial resistance profile. By utilizing the pipeline we developed to investigate the frequency of horizontal resistome transfer, we identified a significantly higher rate of cross-region dissemination compared to localized propagation, highlighting the key role of the resistome in driving the transition and evolutionary history ofS. Gallinarum. Collectively, this study elucidates resistome adaptation in the endemic transition of a single pathogen, providing valuable insights for targeted policy interventions.