Background Pain catastrophizing significantly affects an individual's experience of pain. High pain catastrophizing is associated with increased fear avoidance behaviours, pain intensity and disability. The aim of this investigation was to determine the effect of pain catastrophizing on ongoing brain activity and movement-evoked brain activity during acute orofacial muscle pain. Methods Thirty-four healthy, pain-free subjects were recruited. In 17 subjects, the effect of catastrophizing on regional brain activity was determined. In 19 subjects, functional magnetic resonance imaging was used to determine the effects of pain catastrophizing on brain activation patterns during jaw movements in the presence of ongoing pain. Results We found that in the presence of pain, catastrophizing was significantly correlated with activity in multi-sensory integrative brain regions, including the dorsolateral and medial prefrontal cortices. Importantly, this relationship did not exist when subjects were not experiencing pain. In addition, during repetitive open-close jaw movements in the presence of pain, activity in the primary motor cortex, cerebellar cortex and the trigeminal motor nucleus was positively correlated with pain catastrophizing scores. In contrast, in the dorsolateral prefrontal cortex, as pain catastrophizing scores increased, the magnitude of signal intensity change during jaw movements decreased. Again, no such relationships occurred when the individual was not in pain. Conclusions These data show that during pain, catastrophic thinking has a significant impact on activity in motor and sensory integrative regions. Reducing negative coping strategies may be an effective means in reducing fear avoidance behaviours and the intensity of ongoing pain.