This study investigated the association between area deprivation level and performance of handwashing behavior during the COVID-19 pandemic in Korean adults. This study used data from the 2015 Population and Housing Census data to measure area deprivation level. The 2020 Korea Community Health Survey was used for all other variables, including hand hygiene behavior (August through November 2020). The association between area deprivation level and practice of handwashing behavior was examined using multilevel logistic regression analysis. The study population comprised 215,676 adults aged 19 years or above. Compared to the least area deprived group, the most deprived group was more likely to not wash hands after using the restroom (OR 1.43, 95% CI 1.13–1.82), after coming home (OR 1.85, 95% CI 1.43–2.39), and using soap (OR 1.55, 95% CI 1.29–1.84). The findings suggest the importance of considering area deprivation in implementing policies that promote handwashing, particularly during a pandemic.