It is difficult to conclude that COVID-19 is associated with a decrease in the suicide attempts rate by comparing only a short-term period. Therefore, it is necessary to examine attempted suicide rates through a trend analysis over a longer period. This study aimed to investigate an estimated long-term trend regarding the prevalence of suicide-related behaviors among adolescents in South Korea from 2005 to 2020, including COVID-19. We sourced data from a national representative survey (Korea Youth Risk Behavior Survey) and analyzed one million Korean adolescents aged 13 to 18 years (n=1,057,885) from 2005 to 2020. The 16-year trends regarding the prevalence of sadness or despair and suicidal ideation and attempt and the trend changes before and during COVID-19. Data of 1,057,885 Korean adolescents was analyzed (weighted mean age, 15.03 years; males, 52.5%; females, 47.5%). Although the 16-year trend in the prevalence of sadness or despair and suicide ideation and attempt consistently decreased (prevalence of sadness or despair between 2005-2008, 38.0% with 95% confidence interval CI, 37.7 to 38.4 vs. prevalence in 2020, 25.0% 24.5 to 25.6; suicide ideation between 2005-2008, 21.9% 21.6 to 22.1 vs. prevalence in 2020, 10.7% 10.3 to 11.1; and suicide attempt between 2005-2008, 5.0% 4.9 to 5.2 vs. prevalence in 2020, 1.9% 1.8 to 2.0), the downward slope decreased during COVID-19 (βdiff in sadness, 0.215 with 95% CI 0.206 to 0.224; βdiff in suicidal ideation, 0.245 0.234 to 0.256; and βdiff in suicide attempt, 0.219 0.201 to 0.237) compared with pre-pandemic period. This study found that the observed risk of suicide-related behaviors during the pandemic was higher than expected through long-term trend analysis of the prevalence of sadness/despair and suicidal ideation and attempts among South Korean adolescents. We need a profound epidemiologic study of the change in mental health due to the pandemic's impact and the establishment of prevention strategies for suicide ideation and attempt.