Trajectories of perceived stress from the transition to adulthood (age 25), during young adulthood (age 32), and into midlife (ages 43 and 50) were examined with four waves of longitudinal survey data (N = 688; 49% female, 37% with a university degree, 86% White). We explored how between- and within-person variation in perceived stress was associated with age 50 psychological well-being (life satisfaction and eudaimonic well-being), self-reported physical health, career satisfaction, and intimate partnership satisfaction. Growth curve analyses revealed stress followed a linear decreasing trajectory from the transition to adulthood into midlife with substantial variability underlying the average pattern. Between- and within-person variation in perceived stress was associated with midlife functioning. Those with lower initial levels of and more decline in perceived stress reported better psychological and physical health and higher relationship satisfaction at age 50 compared to those with initially higher perceived stress and less decline over time. Higher than one's own average perceived stress at ages 25, 32, 43, and 50 years was associated with lower psychological and physical health and intimate partnership satisfaction at age 50. These results support key contentions of developmental theory and may prove useful when designing interventions aimed at promoting well-being in midlife.