Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus able to infect humans and multiple nonhuman animal species. Most natural infections in companion, captive zoo, livestock, and wildlife species have been related to a reverse transmission, raising concern about potential generation of animal reservoirs due to human–animal interactions. To date, American mink and white-tailed deer are the only species that led to extensive intraspecies transmission of SARS-CoV-2 after reverse zoonosis, leading to an efficient spread of the virus and subsequent animal-to-human transmission. Viral host adaptations increase the probability of new SARS-CoV-2 variants’ emergence that could cause a major global health impact. Therefore, applying the One Health approach is crucial to prevent and overcome future threats for human, animal, and environmental fields.