To examine the association between cognitive frailty and long-term all-cause mortality and the stratified and combined associations of physical activity and cognitive frailty with long-term all-cause mortality in a population-based cohort of older adults from Spain. A representative cohort of 3677 noninstitutionalized individuals from Spain aged 60 years or older was recruited between April 17, 2000, and April 28, 2001, with follow-up through December 28, 2014. Information on self-reported physical activity and cognitive frailty status were collected at baseline. Analyses were performed with Cox regression after adjustment for confounders. The median follow-up was 14 years (range, 0.03-14.25 years), corresponding to 40,447 person-years, with a total of 1634 deaths. The hazard ratio (HR) for all-cause mortality among participants with cognitive frailty compared with robust participants was 1.69 (95% CI, 1.43-2.01). Being active was associated with a mortality reduction of 36% (95% CI, 21%-47%) in cognitively frail individuals. Compared with those who were robust and active, participants with cognitive frailty who were inactive had the highest mortality risk (HR, 2.13; 95% CI, 1.73-2.61), which was equivalent to being 6.8 (95% CI, 5.33-7.99) years older. Cognitive frailty was more markedly associated with increased mortality in inactive older adults, and being active reduced the mortality risk among cognitively frail individuals by 36%. These novel results highlight that engaging in physical activity could improve survival among cognitively frail older adults.