Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that depression and catastrophizing contributes to TMJD chronicity. This article assesses the effects of catastrophizing and depression on clinically significant TMJD pain (Graded Chronic Pain Scale [GCPS] II–IV). Four hundred eighty participants, recruited from the Minneapolis/St. Paul area through media advertisements and local dentists, received examinations and completed the GCPS at baseline and at 18-month follow-up. In a multivariable analysis including gender, age, and worst pain intensity, baseline catastrophizing (β 3.79, P<0.0001) and pain intensity at baseline (β 0.39, P<0.0001) were positively associated with characteristic of pain intensity at the 18th month. Disability at the 18-month follow-up was positively related to catastrophizing (β 0.38, P<0.0001) and depression (β 0.17, P=0.02). In addition, in the multivariable analysis adjusted by the same covariates previously described, the onset of clinically significant pain (GCPS II–IV) at the 18-month follow-up was associated with catastrophizing (odds ratio [OR] 1.72, P=0.02). Progression of clinically significant pain was related to catastrophizing (OR 2.16, P<0.0001) and widespread pain at baseline (OR 1.78, P=0.048). Results indicate that catastrophizing and depression contribute to the progression of chronic TMJD pain and disability, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with TMJD.