The Mesozoic (Upper Jurassic–Lower Cretaceous) deeply buried gas reservoir play in the central and eastern Gulf coastal plain of the United States has high potential for significant gas resources. Sequence-stratigraphic study, petroleum system analysis, and resource assessment were used to characterize this developing play and to identify areas in the North Louisiana and Mississippi Interior salt basins with potential for deeply buried gas reservoirs. These reservoir facies accumulated in Upper Jurassic to Lower Cretaceous Norphlet, Haynesville, Cotton Valley, and Hosston continental, coastal, and marine siliciclastic environments and Smackover and Sligo nearshore marine shelf, ramp, and reef carbonate environments. These Mesozoic strata are associated with transgressive and regressive systems tracts. In the North Louisiana salt basin, the estimate of secondary, nonassociated thermogenic gas generated from thermal cracking of oil to gas in the Upper Jurassic Smackover source rocks from depths below 3658 m (12,000 ft) is 4800 tcf of gas as determined using software applications. Assuming a gas expulsion, migration, and trapping efficiency of 2–3%, 96–144 tcf of gas is potentially available in this basin. With some 29 tcf of gas being produced from the North Louisiana salt basin, 67–115 tcf of in-place gas remains. Assuming a gas recovery factor of 65%, 44–75 tcf of gas is potentially recoverable. The expelled thermogenic gas migrated laterally and vertically from the southern part of this basin to the updip northern part into shallower reservoirs to depths of up to 610 m (2000 ft).