In this study, the effect of hyperactivity of the lateral pterygoid muscle (LPM) on the temporomandibular joint (TMJ) disk during prolonged clenching was examined with a mathematical model. Finite element models of the TMJ were constructed based on magnetic resonance images from two subjects with or without internal derangement of the TMJ. For each model, muscle forces were used as a loading condition for stress analysis for 10 min clenching. Furthermore, an intermittent increase of the LPM force with intervals of 1 min was applied. In the asymptomatic model, large stresses were found in the central and lateral part of the disk at the onset of clenching. In the retrodiscal tissue, stress relaxation occurred during the first 2 min of clenching. When the force of the LPM increased temporarily, the disk moved anteriorly and returned to its original position afterward. In the symptomatic model, large stresses were observed in both the posterior region of the disk and the retrodiscal tissue throughout clenching. Upon temporary increase of the LPM force, the disk was elongated anteriorly, which appeared to be irreversible. These results indicate that hyperactivity of the LPM may be involved in the progression of disk displacement.