Background: Depression is detrimental to partnership stability. However, it remains unclear if and how the duration and timing of depression affect the risk of family dissolution. Methods: We conducted a Danish register-based cohort study of newly-formed cohabiting and married couples in 2008 and 2009, who were followed from the second year after family formation. Depressive episodes were defined by individual-level prescription patterns of antidepressant drugs (ATC codes N06A) in either partner. Family dissolution was characterized by the discontinuation of a shared residential address. Using Longitudinal Targeted Minimum Loss-based Estimation, we estimated the risk of family dissolution after 5 years of follow-up under various lengths and timings of depressive episodes. Results: There were 102,335 families included. The covariate-adjusted risk of family dissolution in families without depressive episodes was 30.0 % (95 % CI 29.6–30.4 %) and 35.5 % (95 % CI 29.5–41.5 %) in families with at least one depressive episode during follow-up. The risk of family dissolution increased with the duration of depressive episodes to 42.2 % (95 % CI 40.8–43.6 %) for five coherent years of depression. Depression shortly after family formation carried higher risk of family dissolution; this risk was 42.3 % (95 % CI 38.4–46.3 %) for depression experienced in the first year of family formation versus 32.9 % (95 % CI 31.8–34.0 %) in the fifth year of family formation. Limitations: Proxy measures of depression by antidepressant prescriptions fails to identify milder depression. Annual measures of family dissolution precluded more fine-grained analyses of time-intervals. Conclusions: Depression is disruptive to family stability, particularly with longer duration and early onset after family formation.