This study examined the efficacy of adding a remote, synchronous, group, videoconference-based form of Acceptance and Commitment Therapy (ACT) or Behavioral Activation Therapy for Depression (BATD) to treatment-as-usual (TAU) in 234 patients with chronic low back pain (CLBP) plus comorbid depressive symptoms. Participants were randomly assigned to ACT, BATD, or TAU. Compared to TAU, ACT produced a significant reduction in pain interference at post-treatment (d = 0.64) and at follow-up (d = 0.73). BATD was only superior to TAU at follow-up (d = 0.66). A significant reduction in pain catastrophizing was reported by patients assigned to ACT and BATD at post-treatment (d = 0.45 and d = 0.59, respectively) and at follow-up (d = 0.59, in both) compared to TAU. Stress was significantly reduced at post treatment by ACT in comparison to TAU (d = 0.69). No significant between-group differences were found in depressive or anxiety symptoms. Clinically relevant NNT values for reduction in pain interference were obtained at post-treatment (ACT vs TAU = 4) and at follow-up (ACT vs TAU = 3; BATD vs TAU = 5). In both active therapies, improvements in pain interference at follow-up were significantly related to improvements at post-treatment in psychological flexibility. These findings suggest that new forms of Cognitive Behavioral Therapy (CBT) are clinically useful in improving pain interference and pain catastrophizing. Further research on evidence-based change processes is required to understand the therapeutic needs of patients with chronic pain and comorbid conditions. TRIAL NUMBER: NCT04140838 PERSPECTIVE: Group videoconference-based ACT and BATD showed greater efficacy than TAU for reducing pain interference and pain catastrophizing in patients with CLBP plus clinically relevant depression. Psychological flexibility appeared to be the main contributor to treatment effects for both ACT and BATD.