Human enteroviruses (EVs) are associated with a broad spectrum of diseases. To understand EV epidemiology, we present longitudinal data reflecting changing EV prevalence patterns in South Korea. We collected 7160 specimens from patients with suspected EV infections in ten hospitals in Gwangju, Korea during 2011-2020. RNA extraction and real-time reverse transcription polymerase chain reaction using EV-specific probes and primers were performed. EV genotyping and phylogenetic analysis were performed; EVs were detected in 3076 samples (43.0%), and the annual EV detection rate varied. EV infection rates did not differ with sex, and children aged </= 4 years were the most prone to EV infection; this trend did not change over time. Overall, 35 different EV types belonging to four distinctive species and rhinoviruses were identified. Although serotype distribution changed annually, the most frequently observed EVs were EV-A71 (13.1% of the cases), CVA6 (8.3%), CVB5 (7.6%), CVA16 (7.6%), CVA10 (7.5%), E18 (7.5%), E30 (7.0%), and E11 (5.0%) during 2011-2020. The predominant EV genotypes by clinical manifestation were CVB5 for aseptic meningitis; EV-A71 for hand, foot, and mouth disease cases; and CVA10 for herpangina. These results will aid the development of vaccines against EV infection and allow comprehensive disease control.