The aim of the present study was to examine (a) whether a cognitive-behavioral treatment (differentially) affects pain coping and cognition; and (b) whether changes in pain coping and cognition during treatment mediate treatment outcome. Participants in this randomized clinical trial were 148 patients with chronic low back pain attending a multidisciplinary treatment program consisting of operant-behavioral treatment plus cognitive coping skills training (N = 59) or group discussion (N = 58) or allocated to a waiting list control condition (N = 31). Patients improved with respect to level of depression, pain behavior and activity tolerance at posttreatment and 12-month follow-up. Treatment also resulted in a short- and long-term decrease in catastrophizing and an enhancement of internal pain control. Changes in catastrophizing and to a lesser degree in internal pain control mediated the reduction in level of depression and pain behavior following treatment. The use of behavioral and cognitive interventions aimed at decreasing catastrophizing thoughts about the consequences of pain and promoting internal expectations of pain control possibly constitute an important avenue of change irrespective of the type of treatment.