Geodetic leveling observations from Biloxi, MS, to New Orleans, LA, and water level gauge measurements in the New Orleans–Lake Pontchartrain area were analyzed to infer late 20th century vertical motions. These data were used to test the validity of previous subsidence rate measurements and the models that predict the location and causes of subsidence. Water gauges attached to bridge foundations and benchmarks affixed to deep rods that penetrate Holocene strata subsided as much as 0.8 m locally between 1955 and 1995. The observed deep-seated subsidence far exceeds model predictions and demonstrates that shallow processes such as compaction and consolidation of Holocene sediments are inadequate by themselves to explain late 20th century subsidence. Deep-seated subsidence occurring east and north of the normal faults marking the Gulf of Mexico basin margin can be explained by local groundwater withdrawal, and regional tectonic loading of the lithosphere by the modern Mississippi River delta (MRD). Sharp changes in subsidence coincide with strands of the basin margin normal faults. Displacements are consistent with activity and show motions consonant with fault creep. Deep subsidence of the region to the south, including New Orleans, can be explained by a combination of groundwater withdrawal from shallow upper Pleistocene aquifers, the aforementioned lithospheric loading, and perhaps, nongroundwater-related faulting. Subsidence due to groundwater extraction from aquifers ∼160 to 200 m deep dominated urbanized areas and is likely responsible for helping to lower local flood protection structures and bridges by as much as ∼0.8 m.