Millions of barrels of oil escaped into the Gulf of Mexico (GoM) after the 20 April, 2010 explosion of Deepwater Horizon (DH). Ocean circulation models were used to forecast oil slick migration in the GoM, however such models do not explicitly treat the effects of secondary eddy-slopes or Mississippi River (MR) hydrodynamics. Here we report oil front migration that appears to be driven by sea surface level (SSL) slopes, and identify a previously unreported effect of the MR plume: under conditions of relatively high river discharge and weak winds, a freshwater mound can form around the MR Delta. We performed temporal oil slick position and altimeter analysis, employing both interpolated altimetry data and along-track measurements for coastal applications. The observed freshwater mound appears to have pushed the DH oil slick seaward from the Delta coastline. We provide a physical mechanism for this novel effect of the MR, using a two-layer pressure-driven flow model. Results show how SSL variations can drive a cross-slope migration of surface oil slicks that may reach velocities of order km/day, and confirm a lag time of order 5–10 days between mound formation and slick migration, as observed form the satellite analysis. Incorporating these effects into more complex ocean models will improve forecasts of slick migration for future spills. More generally, large SSL variations at the MR mouth may also affect the dispersal of freshwater, nutrients and sediment associated with the MR plume.