Staphylococcus aureus is an important human bacterial pathogen with a wide host range, including livestock, companion, and wild animal species. Genomic and epidemiological studies show that S. aureus can freely transmit between different species, with some of these transmissions resulting in successful adaptation and ongoing transmission in a new species. Given an ever-increasing risk of zoonotic disease emergence due to changes in the humananimal interface, it is increasingly important that we understand the capacity for human pathogens such as S. aureus to move between and adapt to different host species. In this thesis, I apply comparative genomic analyses to investigate the host range, transmission dynamics and host adaptation of S. aureus in livestock, companion animal, and wild animal populations. Chapters 2 and 3 consider the role of horizontal gene transfer in the adaptation of S. aureus clonal-complex (CC) 398 to livestock. CC398 is the dominant S. aureus lineage in European livestock and is implicated in increasing numbers of human infections. I found that the emergence of livestock-associated CC398 coincided with acquiring a Tn916 transposon carrying a tetracycline resistance gene, which has now been stably maintained for 57 years. This was followed by the acquisition of a SCCmec type V that carries methicillin, tetracycline, and heavy-metal resistance genes, which some lineages have maintained for 35 years. In contrast, a phage containing human immune evasion genes is dynamically gained and lost. These contrasting dynamics result in no loss of antimicrobial resistance but the rapid acquisition of the human adaptive element when methicillin-resistant S. aureus (MRSA) jumps from livestock into humans. In later chapters, I address a gap in our understanding of host specificity of S. aureus through using unbiased sampling of both methicillin-sensitive S. aureus (MSSA), and MRSA isolates from both an unsampled wild animal population and an undersampled companion animal species. Chapter 4 investigates the prevalence and risk factors associated with S. aureus carriage in cats in south-eastern Poland. Results suggest that older cats, sick cats, and cats with an S. aureus colonised owner increase the risk of carriage. I then used whole-genome sequences to investigate population structure, showing that S. aureus in cats is diverse and has no dominating lineage. Chapter 5 demonstrates that transmission between cats and their owners can occur within households, and I characterise potential catassociated lineages. In chapter 6, I found no S. aureus isolates in wild populations of brown trout in the Scottish Highlands. This population is phylogenetically divergent from the host species S. aureus is most associated with and is geographically and ecologically isolated. Together these results highlight the considerable transmissibility of S. aureus between host species. Most transmission events that I identify reflect spillover events that are self-limiting in their new populations. Nevertheless, I demonstrate that some level of persistence is common, enough that intermediary hosts can transmit to new species. This highlights the connectedness of S. aureus among different host species and that antimicrobial use in other hosts may impact human health.