The Seno Mexicano (southern Texas, the Burgos Basin, and offshore extensions) is a prolific Cenozoic hydrocarbon province, producing more than 93 TCF and 3.6 billion bbl oil. This study provides the first basin-wide overview of tectonic processes, producing trends, and hydrocarbon systems. The Seno Mexicano overlies highly extended Paleozoic crust; Jurassic salt was deposited across much of the basin. The basin accumulated 1–3 km of Mesozoic deep-water limestone and mudstone. Paleocene eastward tilting formed the Lobo gravity slide and rafted Mesozoic sediments eastward over Jurassic salt to create several deep troughs. Downdip compression is not imaged but must have occurred in the outer coastal zone. Oligocene–Miocene tilting induced the Vicksburg slide, major deltaic progradation, deflation of the Bravo diapir, extrusion of the Sigsbee salt canopy, and compression in two fold belts. Later tilting created a Miocene unconformity and post-Miocene uplift. Major hydrocarbon accumulations occur in seven trends: two Paleocene–Eocene dry-gas trends (the Lobo and Wilcox fault zones [FZs]), two Oligocene gas-condensate trends (the Vicksburg FZ and the Frio FZ), the Eocene Duval oil trend, the Oligocene Nueces oil trend, and the deep-water Perdido (Eocene reservoirs, filled in the Neogene) oil trend. The Seno Mexicano contains Tithonian and Cenomanian–Turonian source rocks and probable Paleocene–Eocene source rocks. Subsidence and maturity modeling show that the dry-gas trends are sourced mostly from mid-Cretaceous units. Gas condensate of the Vicksburg and Frio reservoirs came from Eocene sources in the inner coastal zone. The absence of Miocene production may reflect the lack of Eocene source rock in the outer coastal zone and Bravo trough.