Having a sense of purpose in life has been linked to a reduced risk for several chronic health conditions, though the mechanisms behind this relationship remain underexplored. The present research explored whether purpose in life predicted risk for onset of seven common chronic ailments over an eight year period using data from the Health and Retirement Study. The PROCESS procedure for testing mediation was used to analyse the direct association between purpose and onset of each of the seven chronic conditions, as well as testing whether vigorous and moderate physical activity, sleep quality, and health self-efficacy mediate these relationships. A greater sense of purpose in life was directly associated with a reduced risk for onset of stroke and indirectly associated with a decreased risk for arthritis, heart disease, lung disease, and hypertension onset through its effects on sleep quality.