Background: The coronavirus disease 2019 (COVID-19) pandemic has obviously caused a remarkable change in patients’ emergency department (ED) visits; however, data from multicenter studies are lacking. We aimed to present a comprehensive analysis of injury-related ED visits in Republic of Korea before and during the COVID-19 pandemic. Materials and Methods: Data from 23 tertiary hospitals based on Emergency Department-based Injury In-depth Surveillance were used for this retrospective cross-sectional study. A total of 541,515 ED visits (age ≥ 20 years) between 1 January 2018 and 31 December 2020 were included, and the trend of injuries related to motor vehicular accidents, falls, self-harm and suicide, assault, and poisoning were compared between the pre-COVID-19 time period and during the COVID-19 pandemic. Results: In the first year of the COVID-19 period, a decline in the number of ED visits was observed (41,275, 21%) compared to the previous year. Injuries caused by motor vehicles (36,332 in 2019 vs. 27,144 in 2020), falls and slips (61,286 in 2019 vs. 49,156 in 2020), assaults (10,528 in 2019 vs. 8067 in 2020), and poisonings (7859 in 2019 vs. 7167 in 2020) decreased, whereas self-harm and suicide (8917 in 2019 vs. 8911 in 2020) remained unchanged. The hospitalization (16.6% in 2019 vs. 18.8% in 2020) and ED mortality rate (0.6% in 2019 vs. 0.8% in 2020) also increased. Conclusion: The COVID-19 pandemic led to a decline in the overall number of trauma patients seeking medical care; however, the proportion of patients requiring hospitalization or intensive care unit admission increased, indicating more severe injuries among those who did seek care. Suicide attempt rates remained unchanged, highlighting the need for targeted care and support for vulnerable patients. During the pandemic, EDs had to continue to provide care to patients with medical emergencies unrelated to COVID-19, which requires a delicate and adaptable approach to ED operations. To manage the increased stress and workload caused by the pandemic, increased resources and support for healthcare workers were needed.