Introduction: The family may be negatively impacted by divorce and its adverse outcomes including psychological problems and disturbances in the structure and functioning of families. The present study aimed to determine the efficacy of an online family-based cognitive behavioral therapy (CBT) intervention on psychological distress, family cohesion, and adaptability of divorced head-of-household women. Methods: In this randomized controlled trial, 100 divorced head-of-household women supported by the state welfare organization of Iran participated and were randomly divided into intervention group (n = 50) and active control group (n = 50). Participants in the intervention group received six educational app-based online sessions on family-based CBT. Participants in the control group received an online family-based CBT session and an online information on breast self-examination using the same app. Anxiety, depression, family adaptability, and cohesion were assessed before, immediately after, and 3 months after the intervention. Linear mixed-effects modeling with random intercepts and slopes was used to analyze the data. Results: The mean and standard deviation of measures of anxiety, depression, cohesion, and adaptability scores immediately after the intervention (9.42 +/- 1.78, 9.58 +/- 2.21, 36.36 +/- 3.78, and 36.30 +/- 3.97, respectively) and 3 months after the intervention (9.90 +/- 1.84, 9.40 +/- 1.53, 36.38 +/- 4.30, and 36.42 +/- 4.38, respectively) in the intervention group differed significantly from those before the intervention (11.30 +/- 1.77, 11.56 +/- 1.31, 23.82 +/- 3.78, and 23.80 +/- 3.85, respectively). Changes in the mean scores of anxiety, depression, cohesion, and adaptability variables differed significantly before and immediately after the intervention and before and 3 months after the intervention. Conclusion: Online family-based CBT appears efficacious in improving the psychological status of divorced head-of-household women and the cohesion and adaptability of their families.