Overpressures measured with pore pressure penetrometers during Integrated Ocean Drilling Program (IODP) Expedition 308 reach 70% and 60% of the hydrostatic effective stress lambda* = (u-u(h))/(sigma(nu h)') in the first 200 meters below sea floor (mbsf) at Sites U1322 and U1324, respectively, in the deepwater Gulf of Mexico, offshore Louisiana. High overpressures are present within low permeability mudstones where there have been multiple, very large, submarine landslides during the Pleistocene. Beneath 200 mbsf at Site U1324, pore pressures drop significantly: there are no submarine landslides in this mixture of mudstone, siltstone and sandstone. The penetrometer measurements did not reach the in situ pressure at the end of the deployment. We used a soil model to determine that an extrapolation approach based on the inverse of square route of time (1/root t) requires much less decay time to achieve a desirable accuracy than an inverse time (1/t) extrapolation. Expedition 308 examined how rapid and asymmetric sedimentation above a permeable aquifer drives lateral fluid flow, extreme pore pressures, and submarine landslides. We interpret that the high overpressures observed are driven by rapid sedimentation of low permeability material from the ancestral Mississippi River. Reduced overpressure at depth at Site 1324 suggests suggest lateral flow (drainage) whereas high overpressure at Site 1322 requires inflow from below: lateral flow in the underlying permeable aquifer provides one mechanism for these observations. High overpressure near the seafloor reduces slope stability and provides a mechanism for the large submarine landslides and low regional gradient (2 degrees) offshore from the Mississippi delta.