Recent seismic reflection and ocean bottom seismometer (OBS) studies reveal broad regions of low seismic velocity along the Nankai subduction plate boundary megathrust offshore SW Japan. These low velocity zones (LVZ's) extend ∼55 km landward from the trench, corresponding to depths of >∼10 km below sea floor. Here, we estimate the in-situ pore pressure and stress state within these LVZ's by combining P-wave velocities obtained from the geophysical surveys with new well-constrained empirical relations between P-wave velocity, porosity, and effective mean stress defined by laboratory deformation tests on drill core samples of the incoming oceanic sediment. We document excess pore pressures of 17–87 MPa that extend ∼55 km into the subduction zone, indicating that trapped pore fluids support ∼45–91% of the overburden stress along the base of the upper plate and surrounding major fault zones. The resulting effective stresses in the LVZ are limited to ∼1/3 of the values expected for non-overpressured conditions. These low effective stresses should lead to a mechanically weak and predominantly aseismic plate boundary. The region of lowest effective stress coincides with precisely located very low frequency earthquakes, providing the first quantitative evidence linking these anomalous slip events to low stress and high pore pressure.