On 20 April 2010, while drilling at the Macondo Prospect, situated at the Mississippi Canyon block 252 (MC252), an explosion on the Deepwater Horizon rig caused by a blowout killed 11 crewmen and ignited a fireball visible from 35 miles (56 km) away. Two days later, the rig sank, leaving the well gushing at the seabed and causing the largest offshore oil spill in U.S. history: some 5,000,000 bbl (210,000,000 gal) released into the Gulf of Mexico. The setting of the spill is quite different from other historic marine oil spills that occurred at or near the sea surface. The Deepwater hydrocarbons were released at a depth of ~1,500 m (water pressure ~160 atm) in a high pressure jet (~500 atm), resulting in gas bubbles and liquid oil droplets of different size. Size and chemical composition of the hydrocarbon bubbles and droplets evolved extremely rapidly following release from the well. A complex interplay of physical and biochemical processes determined hydrocarbon-water plume mixing dynamics and affected the composition and spatial distribution of the hydrocarbon mixtures within the water column, at the surface in the resulting oil slick, and in the overlying atmosphere. This presentation considers impact of multiple sources of oil contamination and evaluates the role of different oil weathering processes that change the chemical composition of oil in deep water and their effect on the long-term fate of oil in the Gulf of Mexico coastal waters.