Analysis of 17,141 survivors across seven cancer types reveals that moderate-to-vigorous physical activity after diagnosis reduces cancer-specific mortality by 28% compared to sedentary patients. The protective effect emerged at 7.5 MET-hours weekly—equivalent to 2.5 hours of brisk walking—with benefits plateauing at higher intensities. This represents one of the largest investigations into post-diagnosis exercise across cancers typically excluded from survival studies, including bladder, endometrial, kidney, lung, oral, ovarian, and rectal malignancies. The findings significantly expand evidence beyond breast and colon cancers, where exercise benefits were previously established. Survivors who increased activity levels after diagnosis showed even greater mortality reductions than those maintaining consistent routines, suggesting therapeutic potential for lifestyle interventions during survivorship care. However, the observational design cannot establish causation, and selection bias may favor healthier individuals capable of exercise. The 10.9-year follow-up provides robust long-term data, though results may not generalize to more advanced disease stages. For the growing population of cancer survivors—now exceeding 18 million Americans—these results support integrating structured physical activity into standard survivorship protocols, potentially transforming post-cancer care from passive monitoring to active health optimization.