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Simple Summary: In this study, for the first time in Chile, we compared resistance profiles of Salmonella strains isolated from 4047 samples from domestic and wild animals. A total of 106 Salmonella strains (2.61%) were isolated, and their serogroups were characterized and tested for susceptibility to 16 different antimicrobials. This study reports 47 antimicrobial-resistant (AMR) Salmonella strains (44.3% of total strains). Of the 47, 28 corresponded to single-drug resistance (26.4%) and 19 to multidrug resistance (17.9%). The association between AMR and a subset of independent variables was evaluated using multivariate logistic models. Interestingly, S. Enteritidis was highly persistent in animal production systems; however, we report that serogroup D strains were 18 times less likely to be resistant to at least one antimicrobial agent than the most common serogroup (serogroup B). The antimicrobials presenting the greatest contributions to AMR were ampicillin, streptomycin and tetracycline. Salmonella is a major bacterial foodborne pathogen that causes the majority of worldwide food-related outbreaks and hospitalizations. Salmonellosis outbreaks can be caused by multidrug-resistant (MDR) strains, emphasizing the importance of maintaining public health and safer food production. Nevertheless, the drivers of MDR Salmonella serovars have remained poorly understood. In this study, we compare the resistance profiles of Salmonella strains isolated from 4047 samples from domestic and wild animals in Chile. A total of 106 Salmonella strains (2.61%) are isolated, and their serogroups are characterized and tested for susceptibility to 16 different antimicrobials. The association between antimicrobial resistance (AMR) and a subset of independent variables is evaluated using multivariate logistic models. Our results show that 47 antimicrobial-resistant strains were found (44.3% of the total strains). Of the 47, 28 correspond to single-drug resistance (SDR = 26.4%) and 19 are MDR (17.9%). S. Enteritidis is highly persistent in animal production systems; however, we report that serogroup D strains are 18 times less likely to be resistant to at least one antimicrobial agent than the most common serogroup (serogroup B). The antimicrobials presenting the greatest contributions to AMR are ampicillin, streptomycin and tetracycline. Additionally, equines and industrial swine are more likely to acquire Salmonella strains with AMR. This study reports antimicrobial-susceptible and resistant Salmonella in Chile by expanding the extant literature on the potential variables affecting antimicrobial-resistant Salmonella. [ABSTRACT FROM AUTHOR]