The main pathway of the disablement process consists of four consecutive phases: Pathology (presence of disease/injury), Impairments (dysfunctions/ structural abnormalities), Functional Limitations (restrictions in basic physical/mental actions), and Disability (difficulty doing activities of daily life, ADL). This study determines the presence of the main pathway of disablement in a cohort aged 55 years and older and examines whether progression of the main pathway of disablement is accelerated in the presence of depression. Based on baseline (T1) and two three-year follow-up interviews (T2 and T3) from the Longitudinal Aging Study Amsterdam (LASA) in a population-based cohort of 1110 Dutch persons, we first analysed the intermediate effect of the different consecutive phases of the disablement process by means of multiple regression, adjusted for covariates. Then, depression was used as interaction term in multiple regression analyses linking the consecutive phases of the disablement process. We found that Impairments mediated the association between Pathology and Functional Limitations, and that Functional Limitations mediated the association between Impairments and Disability. Depression significantly modified the associations between Pathology and subsequent Impairments, and between Functional Limitations and subsequent Disability. In sum, the main pathway of the disablement process was identified in our sample. In addition, we found an accelerating effect of depression, particularly in the early and late stages of the model. Reduction of depression may help slow down the process of disablement for persons who find themselves in those stages of the model.