IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic and the policies to contain it have been a near ubiquitous exposure in the US with unknown effects on depression symptoms. OBJECTIVE To estimate the prevalence of and risk factors associated with depression symptoms among US adults during vs before the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS This nationally representative survey study used 2 population-based surveys of US adults aged 18 or older. During COVID-19, estimates were derived from the COVID-19 and Life Stressors Impact on Mental Health and Well-being study, conducted from March 31, 2020, to April 13, 2020. Before COVID-19 estimates were derived from the National Health and Nutrition Examination Survey, conducted from 2017 to 2018. Data were analyzed from April 15 to 20, 2020. EXPOSURES The COVID-19 pandemic and outcomes associated with the measures to mitigate it. MAIN OUTCOMES AND MEASURES Depression symptoms, defined using the Patient Health Questionnaire-9 cutoff of 10 or higher. Categories of depression symptoms were defined as none (score, 0-4), mild (score, 5-9), moderate (score, 10-14), moderately severe (score, 15-19), and severe (score, 20). RESULTS A total of 1470 participants completed the COVID-19 and Life Stressors Impact on Mental Health and Well-being survey (completion rate, 64.3%), and after removing those with missing data, the final during–COVID-19 sample included 1441 participants (619 participants [43.0%] aged 18-39 years; 723 [50.2%] men; 933 [64.7%] non-Hispanic White). The pre–COVID-19 sample included 5065 participants (1704 participants [37.8%] aged 18-39 years; 2588 [51.4%] women; 1790 [62.9%] non-Hispanic White). Depression symptom prevalence was higher in every category during COVID-19 compared with before (mild: 24.6% [95% CI, 21.8%-27.7%] vs 16.2% [95% CI, 15.1%-17.4%]; moderate: 14.8% [95% CI, 12.6%-17.4%] vs 5.7% [95% CI, 4.8%-6.9%]; moderately severe: 7.9% [95% CI, 6.3%-9.8%] vs 2.1% [95% CI, 1.6%-2.8%]; severe: 5.1% [95% CI, 3.8%-6.9%] vs 0.7% [95% CI, 0.5%-0.9%]). Higher risk of depression symptoms during COVID-19 was associated with having lower income (odds ratio, 2.37 [95% CI, 1.26-4.43]), having less than $5000 in savings (odds ratio, 1.52 [95% CI, 1.02-2.26]), and exposure to more stressors (odds ratio, 3.05 [95% CI, 1.95-4.77]). CONCLUSIONS AND RELEVANCE These findings suggest that prevalence of depression symptoms in the US was more than 3-fold higher during COVID-19 compared with before the COVID-19 pandemic. Individuals with lower social resources, lower economic resources, and greater exposure to stressors (eg, job loss) reported a greater burden of depression symptoms. Post–COVID-19 plans should account for the probable increase in mental illness to come, particularly among at-risk populations.