We present the first sequential structural restoration with flexural backstripping of the Gulf of Mexico US‐Mexico conjugate margin salt basin. We construct four large‐scale (100s of km) balanced, sequential structural restorations to investigate spatio‐temporal patterns of subsidence, geometry of the original salt basin, feedbacks between post‐salt structural and stratigraphic evolution, paleo‐bathymetry, and crustal configurations. The restorations are based on interpretations of 2D and 3D seismic data, and include sequential sedimentary decompaction, flexural isostatic backstripping, and thermal isostatic corrections. The spatially variable crustal thinning factor is directly measured from seismic data, and lithologic parameters are determined by well penetrations. We present a model for the original salt basin and discuss evidence for and implications of a deep water salt basin setting for the GoM. Our analysis suggests a salt basin that contained ∼1–2 km thick salt in a basin 175–390 km across with ∼1 km of bathymetry after salt deposition. The base of salt is mostly smooth with <1 km of local relief in the form of normal faults that disrupt a pre‐salt sedimentary section. We find that supra‐salt extension and shortening are not balanced, with measurable extension exceeding shortening by 18–30 km on each cross‐section. Our subsidence analysis reveals anomalous subsidence totaling 1–2 km during Late Jurassic and Early Cretaceous times that may reflect dynamic topography or depth‐dependent thinning. We offer an interpretation of crustal breakup invoking pre‐salt clastic sedimentation, salt deposition in a deep water syn‐thinning basin, and post‐salt lower‐crustal exhumation. Plain Language Summary The Gulf of Mexico is a large basin that formed over 200 million years ago due to tectonically driven extension of a supercontinent. Early in its formation it accumulated thick salt deposits. Due to that salt and the later deposition of several kilometers of sedimentary rock that conceal the deep geology, it is difficult to know exactly how extension started and progressed. This study uses new 2D and 3D seismic data that images the deep geology corresponding to that early extension. We sequentially remove each rock layer to reconstruct what the margin looked like in the Mesozoic. By systematically moving back in time we are able to reconstruct the changing geometry, deformation, and bathymetry of the Gulf of Mexico. Our results reveal periods of time when the bathymetry was influenced by unknown factors, which we posit reflects mantle forces. Key Points We present sequential structural restorations with flexural backstripping of the post‐rift eastern GoM conjugate US‐MX margin from Mesozoic to present We interpret the geometry and bathymetry of the restored Mesozoic salt basin Our analysis indicates significant and widespread Mesozoic anomalous subsidence