A multidrug-resistant strain of Salmonella serotype Typhimurium known as Definitive Type 104 (DT104) has emerged as an increasing case of Salmonella infections in the United Kingdom (UK). DT104 isolates in the UK are highly resistant to antimicrobial agents, frequently demonstrating a pattern of resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline (R-type ACSSuT). This report summarizes surveillance data documenting the rapid emergence of DT104 R-type ACSSuT in the United States and preliminary findings from the investigation of the first outbreak of DT104 infections in this country.