Purpose: This study aims to explore the association between unemployment and depression in people from different age groups ranging from 18 to 65 years old. Methods: This study used a cross-sectional design. We performed bivariate analysis and multivariable logistic regression on the 2010 Behavioral Risk Factor Surveillance System (BRFSS) data from 12 states in the United States. Results: On a sample comprised of n=53,406 individuals, of whom 2,546 (7.8%) were identified as being depressed and 3,448 (10.6%) as unemployed, we found that individuals aged 61~65 years have a lower depression risk compared to those aged 18-25 after adjusting for other variables including employment status. However, people from 61~65 have higher increased risk of depression when unemployed compared to other age groups in all three models tested (3.95 times higher in unemployed people in model 1, and 2.81 times higher in model 2 and model 3). Conclusion Our findings indicate that there may need to be more focus on older adults who are unemployed, with associated support services for their mental health. The results of our study indicate that although older adults are less likely to be unemployed, there are more likely to experience depression if they are unemployed (once other confounding factors are taken into account) than younger adults. Policies and interventions can be developed to address not only the physical difficulties but also the mental challenges with which older adults can be at risk facing in case of unemployment.