Background: Different scales have attempted to assess various aspects of family dynamics and structures. Good family function seems to allow for better prognoses for basic diseases and appears to be a predictor of depression. The aim of this study was to determine the association between family functionality and depression. Methods: This is a systematic review and meta-analysis including cross-sectional, cohort, and case-control studies using validated instruments such as the Family APGAR (Adaptability, Partnership, Growth, Affection, and Resolve) and Family Adaptability and Cohesion Evaluation Scale III. A search strategy was designed for the MEDLINE, Embase, Central, and LILACS databases along with data saturation through a search of unpublished literature from the onset of the databases to the present. The categorical variables are expressed in terms of odds ratios (OR), and the statistical analysis was carried out using Review Manager ver. 5.31 (The Cochrane Collaboration, Oxford, UK) using forest plots with corresponding 95% confidence intervals (CI). A fixed-effect model was used according to the expected heterogeneity, expressed in terms of I 2. The risk of bias was evaluated using the MINORS (methodological index for non-randomized studies) tool. Results: A total of 1,519 studies were found, of which 10 were selected for the qualitative synthesis and four were chosen for the meta-analysis. The result for the association between family dysfunction and depression yielded an OR (95% CI) of 3.72 (2.70 to 5.12) and I 2 of 24%. Conclusion: Family dysfunction and depression are strongly associated.