The rapidly increasing prevalence and spread of antibiotic-resistant Salmonella worldwide have become a thorny problem that poses a serious threat to human health. It is speculated that antibiotic abuse, frequent traveling, and mass gatherings accelerate this threat. To explore this hypothesis, we investigated 13 Salmonella isolates from Medina, Saudi Arabia and 15 from China as the control group using typical methods of serotype identification, antibiotic resistance tests, pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing (MLST). Our results indicated that the isolates from China showed greater serotype diversity and a higher antimicrobial resistance rate, which was consistent with results from other studies in China. In contrast, the Saudi Arabian isolates were mainly identified as Serovar Bredeney and were resistant to a limited number of antibiotics. Interestingly, two of the Bredeney isolates was resistant to third-generation cephalosporins but sensitive to all other tested antibiotics. To confirm the results and understand the underlying molecular mechanisms of these isolates, whole-genome sequencing (WGS) was performed. We discovered that several cephalosporin resistance-associated genes were shared with other strains, but one gene (LEN-23) was unique. Therefore, to the best of our knowledge, we concluded that this study is the first to report the emergence of Salmonella Bredeney resistant to third-generation cephalosporins in Saudi Arabia. © Copyright © 2019 Al kraiem, Zeng, Huo, Yang, Al kraiem, Qin, Cui, Kan, Yan, Yang and Chen.