The Santa Ana area in the Bay of Campeche features a complex Neogene interaction of sedimentation, salt-related deformation, and regional tectonics. We synthesized this interaction using three-dimensional seismic data and logs and paleontological data from six wells. These provide a tectonostratigraphic framework for seven Neogene sequence-stratigraphic boundaries between 12.5 and 1.4 Ma. We analyzed these data using seven isochore maps, two restored cross sections, and a geohistory plot. The Neogene history begins with the Agua Dulce fold belt, which formed between 8.0 and 6 Ma. As the Agua Dulce folding waned, at about 6 Ma, extrusive salt blanketed much of the late Miocene fold belt. Sediment loading began to redistribute this allochthonous salt immediately after the discontinuous canopy was emplaced. Thin overburden sags may have originated as synclines during the waning stages of regional buckling, which also gently deformed the base of the salt canopy. After 3.8 Ma, the mean sedimentation rate more than doubled to 0.7 mm/yr (0.03 in./yr) as sediments became trapped against extensional, mostly counterregional, faults. Between 2.6 and 2.4 Ma, mean aggradation rates increased as much as sixfold to 4 mm/yr (0.16 in./yr) as major extension continued. A north block remained partly starved of sediment whereas depocenters formed proximally because of underlying salt evacuation. After 2.4 Ma, mean aggradation rates fell to 1 mm/yr (0.04 in./yr), probably because the shelf break crossed the study area. The boundary between thick distal sediment and thin proximal sediment shifted northward as the shelf edge prograded. Some depocenters merged in depressions in counterregional hanging walls. After 1.4 Ma, the north and west blocks acted as one, tilting seaward and accommodating the thickest strata.