Lakes Nicaragua and Managua are the two largest lakes in Central America, and they cover a combined area of ~9000 km2 of the presently active Nicaraguan depression and Central America volcanic front. As part of the Subduction Factory focus area of the U.S. National Science “Margins” program, ~1925 km of shallow geophysical data were acquired over Lakes Nicaragua and Managua in May 2006 to establish their late Quaternary structural and stratigraphic history and to better constrain regional models for active tectonics in western Nicaragua, the Gulf of Fonseca, and the Median Trough in El Salvador. In order to investigate regional, upper-crustal deformation resulting from forearc sliver transport and/or slab rollback of the Cocos plate, these new data were integrated with: relocated earthquake epicenters, earthquake focal mechanisms, high-resolution digital topography from the National Aeronautics and Space Administration (NASA) Shuttle Radar Topography Mission (SRTM), published global positioning system (GPS) vectors, onland geologic maps, previous maps of lake bathymetry and bottom sediment types, a previously unpublished regional aeromagnetic data set, and multichannel seismic-reflection profiles from the Gulf of Fonseca and Pacific Ocean. These new data sets have improved bathymetric, bottom sediment, and recent fault maps for both Nicaraguan lakes and can be used as new constraints on the regional geology and tectonics. Three regional structural cross sections across the Nicaraguan depression indicate that the basin is a highly asymmetrical half-graben bounded to the southwest by northeast-dipping, oblique-slip normal faults. Late Oligocene to Holocene extension resulted in footwall uplift along the elevated and folded area of the Nicaraguan Isthmus, and the area of greatest subsidence occurs on the footwall block underlying Lake Nicaragua in the southeast. A similar but younger pattern of footwall uplift adjacent to the down-thrown footwall block is present to the northeast beneath Lake Managua and the Gulf of Fonseca. We interpret this structural pattern as a time-transgressive rift opening, where the oldest extension (late Oligocene–early Miocene) began in the southeast and migrated to the northwest. GPS data indicate that this earlier phase of intra-arc normal rifting is presently being superimposed by arc-parallel, right-lateral shear related to the northwestward transport of the Central America forearc sliver.