Tropical Cyclone (TC) Sally formed on 11 September 2020, traveled through the Gulf of Mexico (GMX), and intensified rapidly before making landfall on the Alabama coast as a devastating category-2 TC with extensive coastal and inland flooding. In this study, using a combination of observations and idealized numerical model experiments, we demonstrate that the Mississippi River plume played a key role in the intensification of Sally near the northern Gulf Coast. As the storm intensified and its translation slowed before landfall, sea surface cooling was reduced along its track, coincident with a pronounced increase in SSS. Further analysis reveals that TC Sally encountered a warm Loop Current eddy in the northern GMX close to the Mississippi River plume. Besides deepening the thermocline, the eddy advected low-salinity Mississippi River plume water into the storm’s path. This resulted in the development of strong upper-ocean salinity stratification, with a shallow layer of freshwater lying above a deep, warm “barrier layer.” Consequently, TC-induced mixing and the associated sea surface cooling were reduced, aiding Sally’s intensification. These results suggest that the Mississippi River plume and freshwater advection by the Loop Current eddies can play an important role in TC intensification near the U.S. Gulf Coast.