Porcine epidemic diarrhea virus (PEDV) is a rapidly evolving virus that causes outbreaks in pig herds worldwide. Mutations in the S protein of PEDV have led to the emergence of new viral variants, which can reduce vaccine immunity against prevalent strains. To understand the infection and variation pattern of PEDV in China, an extensive epidemiological survey was conducted in northeast China from 2015 to 2022. The genetic diversity of enteroviruses co-infected with PEDV and the PEDV S gene was analyzed, common mutation patterns that may have led to changes in PEDV virulence and infectivity in recent years were identified, and structural changes in the surface of the S protein resulting from mutations in the PEDV S gene from 2011 to 2022 were reviewed. Of note, two distinct mutations in the emerging 2022 HEB strain were identified. These findings provide a basis for a better understanding of PEDV co-infection and genetic evolution in northeast China.