Seneca Valley Virus (SVV) infection has recently spread to pig farms in Canada, America, and China. Humans, mice, and houseflies have been identified as hosts and reservoirs. Although such cross-species transmission events are often limited, sustained outbreaks in a new mammalian host can occur. To determine if mink are a new mammalian host of SSV, we studied the molecular characteristics of isolated SVV genomes and analyzed challenge, pathology, and immune response data. The study was the first systemic analysis of a newly isolated strain of SVV from pigs. The strain caused an intestinal infection with associated pathologic changes in mink. SVV stimulated the production of a specific neutralizing antibody. The findings highlight the importance of identifying SVV infection in mink and the host to detect mutated SSV that could threaten livestock and pose public health and economic risks.