Fault zones accommodate relative motion between tectonic blocks and control earthquake nucleation. Nanocrystalline fault rocks are ubiquitous in “principal slip zones” indicating that these materials are determining fault stability. However, the rheology of nanocrystalline fault rocks remains poorly constrained. Here, we show that such fault rocks are an order of magnitude weaker than their microcrystalline counterparts when deformed at identical experimental conditions. Weakening of the fault rocks is hence intrinsic, it occurs once nanocrystalline layers form. However, it is difficult to produce “rate weakening” behavior due to the low measured stress exponent, n, of 1.3 ± 0.4 and the low activation energy, Q, of 16,000 ± 14,000 J/mol implying that the material will be strongly “rate strengthening” with a weak temperature sensitivity. Failure of the fault zone nevertheless occurs once these weak layers coalesce in a kinematically favored network. This type of instability is distinct from the frictional instability used to describe crustal earthquakes.