This prospective study explored the potential mediating role of health-related behavior (alcohol involvement, diet, television viewing, and physical activity) in the association between personality and change in memory performance over 2 years. A nationally representative sample of 8,376 U.K. participants aged 55 years and older (4,572 women, 3,804 men) completed self-report measures of personality and health-related behavior in 2010, and completed a memory performance task in 2010 and 2012. After removing variance associated with potential confounding variables, neuroticism and agreeableness had negative associations, and openness and conscientiousness positive associations with change in memory performance. There were no moderation effects by age, sex, education level, or ethnicity. Multiple mediator models demonstrated that physical activity, television viewing, and alcohol intake mediated associations between personality and change in memory performance. These findings provide evidence that the association between personality and memory performance in older adults can be explained, in part, through health-related behavior.