Despite different health statuses, at least 150 minutes of moderate-intensive exercises per week are recommended to both cancer survivors and adults without cancer histories by the American Cancer Society. This study aimed to (1) assess the effect of physical activity (PA) guidelines adherence on self-rated health (SRH), (2) test whether the effects differ between cancer survivors and adults without cancer histories, and (3) examine whether this difference varies across age groups. Data from the Health Information National Trends Survey 5 (HINTS 5) Cycle 1, 2, and 3 (N = 10,648) was used in this study. Multivariate linear regressions were performed to test the moderation effects of having a cancer history among the total participants and by age groups. Among the total participants, the interaction of cancer history and partial adherence was significant (B = .14, p < .05). Analyses by age groups showed that, among young adults, the interaction of cancer history and full adherence was significant (B =.90, p < .01); among middle-aged adults, no significant interactions were found; among older adults, the interaction of cancer history and partial adherence was significant (B =.17, p < .05). Findings suggest cancer survivors may benefit more than their general-population peers at the same PA guidelines adherence level. The PA guidelines should be recommended to adult cancer survivors across age groups. A reduced amount of PA prescription can be a good alternative when full adherence is not possible or practicable for older cancer survivors due to their capacities and preferences.