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What are the processes that entrapped more than 100 000 tons of emitted petroleum compounds in the deep waters of the Gulf of Mexico during the 2010 Deepwater Horizon disaster? We developed a thermodynamic model of the gas-liquid-water partitioning, densities, and viscosities of petroleum mixtures with varying composition, as a function of pressure, temperature, and water salinity. We incorporated this thermodynamic model into the TAMOC (Texas A&M Oil Spill Calculator) model of the combined buoyant plume dynamics, aqueous dissolution kinetics, and other relevant deep-water effects. This is the first study to demonstrate mechanistically that aqueous dissolution was a major process, with ~27% of the emitted mass dissolved during ascent. Our model predictions also provide insight in the role of the injection of dispersant at the emission source.