The diffusion of Panton-Valentine leukocidin (PVL)-positive methicillin-resistant S. aureus (MRSA) is a health problem in Algeria. The objectives of the study were to investigate the global distribution of methicillin-susceptible S. aureus (MSSA) and MRSA isolates in different ecological niches in this country. In total, 2246 samples were collected from humans, livestock, wild animals, pets, food products and the aquatic environment, from 12 Algerian provinces. A total of 312 S. aureus were detected from 2446 samples (12.7%) in the screened niches. We observed the emergence of toxinogenic S. aureus representing 41% of the isolates. Among them, we noted the diffusion of ST80-IV CA-MRSA PVL + strains isolated in human, animals, and food and genetic diversity of MSSA PVL + isolates. This study suggests an alarming dissemination of MRSA-ST80 PVL + in both human and extra-human sources in Algeria. Moreover, MSSA may become a permanent reservoir of the PVL genes necessary for human infections.