Salmonella enterica serovar Typhimurium is the most common serovar in both human infections and farm animals in Australia and many other countries. High typing resolution is critical for the detection of outbreaks and the investigation of within-patient variation in clinical samples. The combination of SNP typing and next generation genome sequencing opens a new avenue for the application in diagnostic and public health microbiology. In this study, 62 S. Typhimurium genomes were used for identification of the core genome content. The assembled genomes were aligned to the reference strain LT2 using the progressiveMauve. 3846 genes and 1576 intergenic regions were defined as the Typhimurium core genes and proposed for outbreak detection. 45 S.Typhimurium genomes from eight outbreaks were analyzed, including seven strains from HIV-infected adults outbreak in Malawi from 2002 to 2008, 12 isolates from outbreak occurred in Tasmania between 2005 and 2008 and isolates from six outbreaks that derived from the Danish laboratory based surveillance system of human gastrointestinal infections in 2000–2010. SNPs in core genome of S. Typhimurium were extracted on the basis of their genome sequences. The results showed that SNP-tree was sensitive to the outbreak detection, which achieved 100% separation between outbreak isolates, even for the sub-clade of outbreak isolates.This approach is also likely to be useful for other pathogenic bacterial species, providing a more reliable marker for epidemiological analysis.