Prior research indicates that purpose in life and affective stress reactivity are related, and that both relate to allostatic load and cognitive aging. Little is known, however, regarding intraindividual relationships between purpose in life and affective reactivity to perceived stress, as well as the predictive utility of affective reactivity to perceived stress and its rate of change. Therefore, this study examined the time-varying relationship between purpose in life and affective reactivity to perceived stress, the trajectory of affective reactivity to perceived stress as it relates to both within- and between-person purpose in life, as well as the predictive utility of affective reactivity to perceived stress and its rate of change on later life cognitive ability and allostatic load. The current sample comprised 933 participants from the Notre Dame Study of Health & Well-being, a 10-year study of annual questionnaire packets paired with biennial, 56-day daily diary bursts. Analyses included three-level multilevel models from which random effects were extracted and used in multiple regression models to predict allostatic load and cognitive ability. Results indicated that individuals were affectively reactive to perceived stress, and that affective reactivity to perceived stress declined across the study period. In terms of the effects of purpose in life on these processes, there were two cross-level interaction effects indicating that (1) individuals who were more purposeful tended to be less stress reactive than individuals who were less purposeful, and (2) individuals who were more purposeful tended to decline less in negative affect across the study period than individuals who were less purposeful. There was also preliminary evidence for a within-person interaction effect between yearly purpose in life and daily affective reactivity such that when individuals felt particularly purposeful, they also tended to be slightly less stress reactive. Finally, higher affective reactivity to perceived stress, as well as less decline in this construct, was predictive of better cognitive ability. These findings indicate that purpose in life may buffer against environmental and maturational effects on negative affect, and that affective reactivity to perceived stress may indicate a different, more adaptive process than affective reactivity to experienced stressors.