People with a greater sense of purpose in life may be more likely to engage in physical activity. At the same time, physical activity can contribute to a sense of purpose in life. The present research tests these hypotheses using a cross-lagged panel model in a nationally representative, longitudinal panel of American adults (N = 14,159, Mage = 68). An increase in sense of purpose in life was associated with higher physical activity four years later, above and beyond past activity levels. Physical activity was positively associated with future levels of sense of purpose in life, controlling for prior levels of purpose in life. Results held in a second national panel from the US with a nine-year follow-up (N = 4,041, Mage = 56). The findings demonstrate a bidirectional relationship between sense of purpose in life and physical activity in large samples of middle-aged and older adults tracked over time.