We examined whether the relationship between activities of daily living and quality of life was mediated by depression, and identified differences of the mediating effects by age group. In this cross-sectional survey, 231 older adults were recruited from eight nursing homes. The path analysis indicated that depression played an important mediating role in the relationship between activities of daily living and quality of life. Depression appeared to be more significant for the mental health component as an outcome compared to the physical health component of quality of life. The impact of depression as a mediator for the older old group was greater than the young-middle group. This finding increases our understanding of the impact of age on the mediating effect of depression on the relationship between activities of daily living and quality of life. Healthcare providers should consider older adults' age differences when integrating physical or depression programs into clinical practice to enhance quality of life.