Salmonella Minnesota has emerged in Brazil as the predominant serovar in poultry and poultry products, along with Salmonella Heidelberg. To understand the emergence of Salmonella Minnesota over the last few years in Brazil, we performed a comparative analysis between 69 selected S. Minnesota genomes from Pathogen Detection database and 65 clonal emergent genomes isolated from Brazil. We demonstrate the presence of multidrug resistance genes against tetracycline [tet(A)], sulfonamide (sul2), and AmpC beta-lactamase (blaCMY-2) in emergent genomes, along with the carriage of a megaplasmid of resistance and virulence (~210 kb), designated pESM (plasmid for emergent Salmonella Minnesota). pESM is an IncC/A2 plasmid predicted to increase S. Minnesota environmental tolerance to mercury (mer operon) and provide resistance to tetracycline and ampicillin due to the presence of tet(A) and blaCMY-2, respectively. Moreover, pESM carries the yersiniabactin siderophore (high-pathogenicity island of Yersinia) related to the iron uptake. The temporal inference demonstrated that the most recent common ancestor dated from ~1978 and that the clonal emergent genomes carrying the pESM belong to a completely different lineage of S. Minnesota. Our results indicate that the presence of pESM likely contributes to the emergence of S. Minnesota and is precisely related to the successful spread of this particular clonal lineage in Brazil.IMPORTANCESalmonella Minnesota has emerged in Brazil as one of the leading serovars related to human and animal infection, presenting high virulence and antibiotic resistance to drugs classified as the highest priority for clinical treatment in humans. This study performed whole-genome sequencing, temporal analysis, and phylogenetics to understand the genetic insights related to the emergence of Salmonella Minnesota in Brazil. Long-read sequencing has led to the identification and characterization of a unique megaplasmid carrying virulence, antibiotic resistance, and heavy-metal tolerance genes, which may play a central role in S. Minnesota's successful emergence in Brazil and possibly worldwide. The potentially high transmissibility of this plasmid between clones and serovars represents a risk to public health since its acquisition may increase Salmonella's fitness, virulence, resistance, and persistence. Understanding the genetic aspects related to the emergence of serovars can help devise measures to mitigate the spread of hazardous multidrug-resistant strains.