Purpose <p>Breast cancer survivors are at increased risk of poor health-related quality of life (HRQOL). Clinical trials suggest physical activity interventions may improve HRQOL, however, evidence on whether these benefits extend to physical activity in real-world settings is limited. We aimed to evaluate the association between post-diagnosis recreational physical activity and HRQOL among breast cancer survivors in the observational literature and compare findings with clinical trial data.</p> Methods <p>A systematic review was conducted, searching seven databases for studies published between January 2003 and October 2024. Study characteristics and adjusted analyses of the association between recreational physical activity and HRQOL were extracted. A qualitative synthesis categorized HRQOL outcomes into global, physical, emotional, social, and breast cancer-specific domains. Risk of bias was assessed, and findings from observational studies were compared with those from clinical trials.</p> Results <p>The search identified 5831 sources, with 11 studies meeting inclusion criteria. For most domains, studies reported positive associations between aerobic activity and HRQOL. Meeting aerobic activity guidelines was found to have clinically meaningful positive associations with global HRQOL (Five studies), physical HRQOL (Two studies), and breast cancer-specific HRQOL (One study). Fewer studies reported on emotional/social domains of HRQOL or the association between muscle-strengthening activity and HRQOL. Overall, observational findings were consistent with clinical trial findings.</p> Conclusions <p>Observational evidence suggests that aerobic activity guideline adherence may be associated with increased global and physical HRQOL. These findings indicate that benefits observed in trials may extend to real-world recreational aerobic activity. Further research is needed on muscle-strengthening activity and activity dosage.</p>