We use two-dimensional fluid flow and slope stability models to study the evolution of overpressure and slope stability in the Ursa region, northern Gulf of Mexico. Our model predictions match measured overpressures from Integrated Ocean Drilling Project Expedition 308 Site U1324 above 200 mbsf, but overpredicts deeper overpressures by 0.4-1.1 MPa. Slope stability models predict a slope failure at 61 ka on the eastern end of the Ursa region. This predicted failure corresponds to a mass transport deposit (MTD) that has been interpreted as a retrogressive failure initiated by high overpressure. Overpressure alone could not drive failure of a second MTD at ~27 ka. We predict that a magnitude 5 earthquake within 140 km of the Ursa region would initiate this failure. We conclude that overpressure could drive submarine slope failures and horizontal acceleration from earthquakes can further facilitate this process.