Background/Objectives: The strict preventive measures implemented globally during the COVID-19 pandemic affected mental health, with most countries reporting a rise in depression and suicide. This study examined factors affecting depression among Korean adults based on quarantine experiences during 2020 and identified key areas for mental health support. Methods: Data were obtained from South Korea’s 2020 Community Health Survey. Responses from 219,228 adults (1893 with quarantine experience and 217,335 without) to questions about quarantine experience, depression (Korean version of PHQ-9 score ≥ 10 or a response of ‘several days’ or more on item 9), and individual/environmental factors were analyzed. Complex sampling analysis, including descriptive statistics and logistic regression, was conducted using SPSS 29.0. Results: This study found that 158 (weighted 7.5%) of those with quarantine experience, and 12,833 (weighted 5.8%) without quarantine experience, reported depression. Regardless of quarantine, being female, having a low income, a history of depression, and increased stress were associated with a higher depression rate, while good subjective health was linked to lower depression rates. Smoking, living-alone, and a lack of sleep among non-quarantined individuals were linked to increased depression risk, while adequate physical activity was linked to reduced risk. Interestingly, alcohol consumption and being overweight (BMI 23–<25) were associated with lower depression rates. Environmental factors, like unmet medical needs and reduced daily activity, were linked to increased depression. Strong social support and social distancing adherence were associated with reduced depression. Conclusions: These findings underscore the importance of targeted interventions considering quarantine experiences to reduce depression during pandemics.