The strengths of crustal faults inferred from borehole-derived heat-flow measurements and maximum stress orientations are lower than those determined from laboratory measurements. Because long-term changes of fault strength cannot be directly monitored using geophysical techniques, the causes of fault weakening are not well understood. We provide laboratory evidence that supports the view that long-term weakening of the frictional strength of faults is caused by microfracturing at asperity contacts, which is a result of crack growth at subcritical stress levels. We conducted triaxial compression tests on mylonite samples at successively higher temperatures from room temperature to 600°C to accelerate reaction processes so that they were observable at laboratory time-scales. Our results suggest that long-term reductions of fault strength are related to chemical reactions that take place in the presence of water. In the presence of water, frictional strength decreased as temperature increased, whereas it changed little in the absence of water. Thus, the presence of fluids has an important influence on changes of fault strength, and it is not only high fluid pressure that is important.