Depression is a growing public health concern in Ghana, exacerbated by limited mental health services, stigma, and socio-economic disparities. While awareness is rising, research on its prevalence, health-seeking behavior, and socio-economic determinants remains limited. This study estimates depression prevalence, assesses health-seeking behavior, and identifies socio-economic drivers influencing these outcomes. Using three waves of the Ghana Socioeconomic Panel Survey (2009/2010, 2013/2014, 2018/2019), depression was measured via the Kessler Psychological Distress Scale (K10). Logistic regression and random-effects models analyzed the socio-economic factors affecting depression and mental health-seeking behavior. Depression prevalence declined from 31.04% in 2009/2010 to 27.21% in 2013/2014 but rose again to 29.54% in 2018/2019. Health-seeking behavior improved from 6.38 to 14.88%, though rural and disadvantaged groups remained underserved. Older adults (65+) and Northern Region residents had significantly higher odds of depression, while post-secondary education reduced risk. Unemployment correlated with lower depression odds, likely reflecting the protective role of communal networks in Ghana. Depression remains a significant issue, with persistent disparities in access to care. Expanding rural mental health services, improving mental health literacy, and addressing regional inequalities are crucial to reducing Ghana's mental health burden.