Objective: Chronic stress has well-documented negative effects on hippocampal structure and function, and has been suggested to contribute to age-related declines. In contrast, there is evidence that exercise has beneficial effects in older adults. The current investigation examined effects of lifetime stress on hippocampal volume and memory, the moderating role of stress on age effects, and the moderating role of exercise on stress-related effects. Method: Measures of lifetime stress, exercise engagement, magnetic-resonance-imaging-based volumes, and cognitive performance were obtained in a sample of healthy middle-aged and older adults. Results: There was a significant negative influence of stress on hippocampal volume. In addition, exercise engagement moderated effects of lifetime stress on both hippocampal volume and memory. Specifically, lower exercise engagement individuals evidenced greater stress-related declines compared with high exercise engagement individuals. Conclusions: These novel findings suggest that benefits of exercise in later adulthood may extend to minimizing detrimental effects of stress on the hippocampus and memory.