The pressure of deep fluids in subduction zones is a major control on plate boundary strength and earthquake genesis. The record, by methane-rich fluid inclusions, of large (~ 50–100 MPa) and instantaneous pressure variations in the Shimanto Belt (Japan) points to the presence of large fluid overpressure at depth (300–500 MPa, ~ 250 °C). To further analyze the connection between methane and fluid overpressure, we determined with Rock-Eval the potential for a worldwide selection of deep seafloor sediments to produce methane as a result of organic matter (OM) cracking due to temperature increase during subduction. The principal factor controlling the methanogenesis potential of sediments is OM proportion, while OM nature is only a subordinate factor. In turn, OM proportion is mainly controlled by the organic terrigenous input. Considering a typical sediment from ocean-continent subduction zones, containing 0.5 wt% of type III OM, cracking of OM has two major consequences: (1) Methane is produced in sufficient concentration as to oversaturate the pore-filling water. The deep fluid in accretionary prisms is therefore a mechanical mixture of water-rich and methane-rich phases; (2) CH4 production can generate large fluid overpressure, of the order of several tens of MPa, The conditions for these large overpressure are a low permeability of the upper plate (< 2.10− 21 m2) and décollement zone (< 10− 18 m2), which may be prevailing in the depth domain (z > 10 km) where OM thermal cracking occurs. At these depths, OM thermal cracking appears as a source of overpressure larger than the last increments of smectite-to-illite reaction. Such large overpressures play potentially a role in facilitating slip along the plate interface. Conversely, the scarcity of earthquakes in ocean-ocean subduction zones such as Marianna or Barbados may be related to the low influx of detrital OM and the limited methane/overpressure generation at depth.