Increasing evidence suggests positive associations between physical activity, social support, and quality of life in later life. However, the role of physical activity and social support in the influence on quality of life is unclear. In this viewpoint, definitions of central terms and key research findings on factors influencing quality of life in older adults are provided. We highlight the importance of both a physically active lifestyle and high social support in positively influencing quality of life. However, we question the direct effect of physical activity on quality of life and present data of a cross-sectional study to support the assumption that the effect of physical activity on quality of life might be influenced by perceived social support. In this cross-sectional study, self-reported physical activity, social support, and quality of life were assessed in a nonclinical sample of 100 adults aged between 60 and 80 years. Statistical analyses included correlation analyses and covariate-controlled mediation analyses. The results confirmed the research findings on positive correlations between all domains of quality of life and both physical activity and social support. Mediation analyses indicated that the effect of physical activity on all domains of quality of life was at least partially mediated by social support, when controlled for covariates. Based on the findings of published evidence and this cross-sectional study, a socially and physically active lifestyle is recommended for older adults to positively influence quality of life. However, the well-documented effect of physical activity on quality of might be an at least partially mediated effect by perceived social support. Practical and research-related implications of a potential indirect effect are discussed. Further prospective research is warranted to clarify the relationship between the variables.