Background: The mortality benefits of meeting the US federal guidelines for physical activity, which includes recommendations for both aerobic and muscle-strengthening activities, have never been examined among smokers. Our aim was to investigate the association between reporting to meet the guidelines and all-cause, cancer, cardiovascular disease, and respiratory disease mortality among smokers. Methods: We pooled data from the 1998–2009 National Health Interview Survey, which were linked to records in the National Death Index (n = 68,706). Hazard ratios (HR) were computed to estimate the effect of meeting the physical activity guidelines on mortality. Results: Smokers who reported meeting the guidelines for physical activity had 29% lower risk of all-cause mortality (HR: 0.71; 95% confidence interval [CI], 0.62–0.81), 46% lower risk of mortality from cardiovascular disease (HR: 0.54; 95% CI, 0.39–0.76), and 26% lower risk of mortality from cancer (HR: 0.74; 95% CI, 0.59–0.93), compared with those who reported meeting neither the aerobic nor the muscle-strengthening recommendations of the guidelines. Meeting the aerobic recommendation of the guidelines was associated with a 42% decline in that risk (HR: 0.58; 95% CI, 0.44–0.77). Conclusion: Smokers who adhere to physical activity guidelines show a significant reduction in mortality.