BACKGROUND: The absence of effective antiviral medications and vaccines increased the focus on non-pharmaceutical preventive behaviors for mitigating against the coronavirus disease 2019 (COVID-19) pandemic. To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea. METHODS: This was a serial cross-sectional population-based study in Korea with four surveys conducted on June 2 and 25, 2015 (MERS-CoV surveys), and February 4, and April 2, 2020 (COVID-19 surveys). Of 25,711 participants selected using random digit dialing numbers, 4,011 participants (aged >/= 18 years) were successfully interviewed, for the 2020 COVID-19 (n = 2,002) and 2015 MERS-CoV (n = 2,009) epidemics were included. Participants were selected post-stratification by sex, age, and province. The total number of weighted cases in this survey equaled the total number of unweighted cases at the national level. We measured the levels of preventive behaviors (social distancing [avoiding physical contact with others]), and practicing transmission-reducing behaviors such as wearing face mask and handwashing. RESULTS: Between the surveys, respondents who reported practicing social distancing increased from 41.9%-58.2% (MERS-CoV) to 83.4%-92.3% (COVID-19). The response rate for the four surveys ranged between 13.7% and 17.7%. Practicing transmission-reducing behaviors (wearing face masks and handwashing) at least once during COVID-19 (78.8%, 80.2%) also increased compared to that during MERS-CoV (15.5%, 60.3%). The higher affective risk perception groups were more likely to practice transmission-reducing measures (adjusted odds ratio, 3.24-4.81; 95 confidence interval, 1.76-6.96) during both COVID-19 and MERS-CoV. CONCLUSION: The study findings suggest markedly increased proportions of non-pharmaceutical behavioral practices evenly across all subgroups during the two different novel virus outbreaks in Korea. Strategic interventions are needed to attempt based on preventive behavior works.