Chronic low back pain (CLBP) is an urgent global health priority given its high prevalence and impact as the leading cause of disability. While several efficacious treatments exist, most have modest effects. Improving outcomes requires a better understanding of treatment mechanisms to enable optimisation. This study explored the mechanisms of cognitive functional therapy (CFT), a biopsychosocial intervention with large, durable effects for adults with disabling CLBP. A longitudinal mediation analysis was performed on data from the RESTORE multisite clinical trial comparing CFT (n = 327) to usual care (n = 165). Mediators (self-efficacy, fear, catastrophising, and pain intensity) were specified based on behavioural theories underlying CFT and previous research. The joint mediation of treatment effects on disability (Roland Morris Disability Questionnaire) and pain intensity (numerical rating scale), were examined using a counterfactual framework for mediation analysis. As hypothesised, earlier changes in self-efficacy, fear, catastrophising, and pain intensity mediated improvements in disability at the end of treatment and at 12-month follow-up, explaining up to 61 % of the effect. Similarly, self-efficacy, fear, and catastrophising mediated the effect of CFT on pain intensity, explaining up to 62 % of the effect. Results are consistent with previous CLBP mediation research highlighting self-efficacy, fear, and catastrophising as likely common mechanisms among effective biopsychosocial treatments. CFT demonstrates large, durable, and clinically important effects on these mechanisms. Findings shed light for clinicians and researchers on how CFT works, although the role of other mechanisms such as movement changes requires further exploration, along with research analysing how different treatment components activate these mechanisms.