Abstract Purpose Existing evidence on the mental health consequences of disadvantaged areas uses cross-sectional or longitudinal studies with short observation periods. The objective of this research was to investigate this association over a 69-year period. Methods Data were obtained from the MRC National Survey of Health and Development (NSHD; the British 1946 birth cohort), which consisted of 2125 participants at 69 years. We assessed longitudinal associations between area disadvantage and mental health symptoms at adolescence and adulthood with use of multilevel modelling framework. Results After adjustment for father’s social class, for each one percentage increase in area disadvantage at age 4, there was a 0.02 (95% CI 0.001, 0.04) mean increase in the total score of the neuroticism scale at age 13–15. After adjustment for father’s social class, adult socio-economic position, cognitive ability and educational attainment, a one percentage increase in change score of area disadvantage between age 4 and 26 was associated with a mean increase in the total Psychiatric Symptom Frequency score (MD 0.06; 95% CI 0.007, 0.11). Similar associations were observed with change scores between ages 4, 53, 60 and total General Health Questionnaire-28 score at age 53 (MD 0.05; 95% CI 0.01, 0.11) and 60–64 (MD 0.06; 95% CI 0.009, 0.11). Conclusions Cohort members who experienced increasing area disadvantage from childhood were at increased risk of poor mental health over the life course. Population-wide interventions aiming at improving social and physical aspects of the early neighbourhood environment could reduce the socio-economic burden of poor mental health.