In this study, we examine the association between social frailty and depression among older adults in Ghana over time. We employed longitudinal data analysis to examine the association between social frailty, socioeconomic status and depression using data from the WHO-SAGE survey. Our descriptive and cross-tabulation analyses show that the prevalence of depression and social frailty among older adults decreased considerably in 2014/2015 compared to 2007/2008. The finding also reveals a huge reduction in social frailty among older adults in northern Ghana–the most deprived regions in Ghana–compared to those in southern Ghana. The multivariate panel data analysis reveals that depression was significantly associated with social isolation, financial needs, and physical needs. The findings suggest an over time decline in social frailty and depression among older adults, as well as, reduction in regional differences in social frailty and depression among older adults in Ghana.