Background: With deteriorating eyesight, people often become dependent on others for many aspects of their daily lives. As a result, they feel less ‘in control’ and experience lower self-esteem. Lower sense of mastery and self-esteem are known to predict depression, but their roles in people with visual impairment have only marginally been investigated. Therefore, this study aimed to determine the influence of mastery and self-esteem on the relationship between visual acuity and mental health.Methods: A longitudinal cohort study was performed using data from the Longitudinal Aging Study Amsterdam (LASA), collected between 2001 and 2012. A community-based population of 2599 older adults (mean age 72 years) were included, who were randomly selected from population registers. Outcomes of interest were the Pearlin Mastery Scale, Rosenberg Self-Esteem Scale, Center for Epidemiologic Studies – Depression scale and the Hospital Anxiety Depression Scale – Anxiety subscale. Linear mixed models were used to establish the association between visual acuity and mental health over time.Results: Mean age was 72 years, 56% was female and 1.2% qualified as having low vision. Visual impairment was associated with a lower sense of mastery (β = -0.477, p < 0.001), lower self-esteem (β = -0.166, p = 0.008) and more depression (β = 0.235, p < 0.001). No significant association between visual acuity and anxiety was found. The relationship between visual acuity and depression was mediated by self-esteem (25%) and sense of mastery (79%).Conclusions: Vision loss was associated with depression. This association was mediated by self-esteem and sense of mastery. This provides us with new possibilities to identify, support and treat those at risk for developing depression by aiming to increase their self-esteem and sense of mastery.