Detection of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) across a broad mammalian host range has prompted concern that parallel evolution of SARS-CoV-2 in animals could reignite a surge in human infection. We conducted surveillance studies to describe the coronaviral landscape of wild and domestic animals (n = 889; 27 species) in the Northeastern United States. We focused on the white-footed mouse (WFM) and supplemented surveillance with laboratory infection studies to assess intra-and interspecies transmission of ancestral and Omicron variants. We detected a range of coronaviruses in fecal swabs, oral swabs or stool specimens from seven species. We did not detect SARS-CoV-2 in any animal. Infection of WFM with SARS-CoV-2 confirmed their susceptibility to ancestral and Omicron variants, however viral RNA shedding declined with the latter. Intraspecies transmission was achieved only with the ancestral strain. Neither strain could be transmitted across species. Free-living WFM experienced a 4% infection rate with a recently described Peromyscus Betacoronavirus with high similarity to HCoV-OC43. We failed to achieve in vivo infection of WFM with HCoV-OC43 indicating that WFM are unlikely to transmit this virus. Our data support a model in which evolution of SARS-CoV-2 in humans may be accompanied by its declining foothold within the animal virome.