Background: Cognitive-attentional syndrome (CAS) is one of the primary constructs of depression, the treatment of which is highly challenging because of its high prevalence and the emergence of symptoms such as feelings of sadness, emptiness, and hopelessness. Objectives: The present study aimed to investigate the effectiveness of behavioral activation (BA) and acceptance and commitment therapy (ACT) in CAS in patients with depression. Methods: This quasi-experimental research utilized a pretest, posttest, and two-month follow-up design with a control group. The study population comprised 260 patients with a diagnosis of depression who referred to the psychological centers of Ahvaz in 2019. The sample consisted of 45 patients with depression selected by convenience sampling. We randomly divided the participants into two experimental groups (BA and ACT) and a control group (n = 15 per group). The research instrument included the cognitive-attentional syndrome (CAS-1) questionnaire. Data were analyzed using SPSS version 24.0 with descriptive and inferential statistics, such as mean, standard deviation, and multivariate analysis of covariance (MANCOVA). Results: In terms of CAS and its components, there was a significant difference between the experimental and control groups in the posttest and follow-up phases (P = 0.0001). Besides, ACT and BA significantly reduced CAS and its components in the posttest phase (P = 0.0001). However, the effectiveness of BA in decreasing CAS and its components remained during the follow-up phase. Furthermore, the results showed that ACT was more effective in reducing attention to threat and metacognitive beliefs during the posttest phase. Conclusions: According to research findings, both BA and ACT are efficient therapies in reducing CAS in patients with depression. Thus, both approaches can be used to strengthen treatment interventions to reduce CAS in patients with depression.