Methicillin-resistant Staphylococcus aureus (MRSA) remains an important etiological factor of human and animal infectious diseases, causing significant economic losses not only in human healthcare but also in the large-scale farming sector. The constantly changing epidemiology of MRSA observed globally affects animal welfare and raises concerns for public health. High MRSA colonization rates in livestock raise questions about the meaning of reservoirs and possible transmission pathways, while the prevalence of MRSA colonization and infection rates among companion animals vary and might affect human health in multiple ways. We present the main findings concerning the circulation of animal-associated MRSA (AA-MRSA) in the environment and factors influencing the direction, mechanisms, and routes of its transmission. Studies have shown it that S. aureus is a multi-host bacterial pathogen; however, its adaptation mechanisms enabling it to colonize and infect both animal and human hosts are still rarely discussed. Finally, we elaborate on the most successful strategies and programs applied limiting the circulation of AA-MRSA among animals and humans. Although MRSA strains colonizing animals rarely infect humans, they undergo host-adaptive evolution enabling them to spread and persist in human populations.