Cancer is most often a disease of aging, and frequently, a disease for which obesity serves as a risk factor. Thus, many cancer survivors are older, overweight or obese, with higher illness burden, symptoms, and comorbidities. Against this backdrop, survivors are at increased risk for functional decline. The question is whether lifestyle interventions can still benefit older, sicker survivors? The purpose of this study was to examine how overweight long-term survivors' symptom severity prior to a diet and exercise intervention is associated with post-intervention function and to determine symptoms' effects on function through change in physical activity, diet quality, and weight status. Methods This is a secondary data analysis of 514 breast, prostate, and colorectal cancer survivors who participated in the one-year home-based diet and exercise intervention, Reach-Out to Enhance Wellness (RENEW) trial. Pre- and post-intervention data were analyzed. Measures of this study included pre-intervention symptoms, changes in weight, physical activity, diet quality, and post-intervention overall physical function (PF), and basic and advanced lower extremity function (BLEF and ALEF). Simple and serial mediation analyses were conducted to examine direct effects of symptom severity on BLEF and ALEF and the indirect effects of symptom severity through changes in diet quality, physical activity, and weight status. Results Increased symptom severity was directly associated with lower functioning scores for PF (b = -0.63 P < 0.001), BLEF (b = -0.33, P < 0.001) and ALEF (b = -0.22, P < 0.001). Indirect effects of symptom severity through weight loss, physical activity and diet were not significant. Weight loss and increased physical activity were significantly associated with higher PF and ALEF and higher diet quality was associated with higher BLEF. Conclusion Symptom severity of older, overweight cancer survivors negatively affects physical function. However, greater weight loss and physical activity were associated with higher functioning scores, regardless of symptom severity. Findings build from the recent emphasis on the negative effects of obesity on survivor outcomes to highlight weight loss as an important factor in maintaining function in older cancer survivors.