The emergence of antimicrobial resistance (AMR) and multidrug resistance (MDR) among microorganisms to commonly used antibiotics is a growing concern in both human and veterinary medicine. Companion animals play a significant role in the epidemiology of AMR, as their population is continuously increasing, posing a risk of disseminating AMR, particularly to strains of public health importance, such as methicillin-resistant Staphylococcus strains. Thus, this study aimed to investigate the prevalence of AMR and MDR in commensal and infection-causing Staphylococcus spp. in dogs and cats in Valencia region. For this purpose, 271 samples were taken from veterinary centers to assess antimicrobial susceptibility against 20 antibiotics, including some of the most important antibiotics for the treatment of Staphylococcus infections, including the five last resort antibiotics in this list. Of all the samples, 187 Staphylococcus spp. strains were recovered from asymptomatic and skin-diseased dogs and cats, of which S. pseudintermedius (≈60%) was more prevalent in dogs, while S. felis (≈50%) was more prevalent in cats. In the overall analysis of the isolates, AMR was observed for all antibiotics tested, including those crucial in human medicine. Furthermore, over 70% and 30% of the strains in dogs and cats, respectively, exhibited MDR. This study highlights the significance of monitoring the trends in AMR and MDR among companion animals. The potential contribution of these animals to the dissemination of AMR and its resistance genes to humans, other animals, and their shared environment underscores the necessity for adopting a One Health approach.