Although many of the current hypotheses to explain the origin and distribution of the Amazon biodiversity has been based directly or indirectly on geological data, the reconstruction of the geological history of the Amazon region is still inadequate to analyze its relationship with the biodiversity. This work has the main goal to characterize the sedimentary successions formed in the Brazilian Amazon in the Neogene-Quaternary discussing the evolution of the depositional systems through time and analyzing their main controlling mechanisms in order to fill up this gap. Radar image interpretation, sedimentological studies, and radiocarbon dating allowed the mapping of Plio-Pleistocene to Holocene units along the Solimões-Amazonas River, Brazil. This integrated work led to the characterization of five sedimentary successions overlying Miocene deposits of the Solimões/Pebas Formation, which include the following: Içá Formation (Plio-Pleistocene), deposits Q1 (37,400–43,700 14C yr B.P.), deposits Q2 (27,200 14C yr B.P.), deposits Q3 (6730–2480 14C yr B.P.), and deposits Q4 (280–130 14C yr B.P.). These deposits occur mostly to the west of Manaus, forming NW–SE elongated belts that are progressively younger from SW to NE, indicating a subsiding basin with a depocenter that migrated to the NE. The reconstruction of the depositional history is consistent with significant changes in the landscapes. Hence, the closure of a large lake system at the end of the Miocene gave rise to the development of a Plio-Pleistocene fluvial system. This was yet very distinct from the modern drainage, with shallow, energetic, highly migrating, braided to anastomosed channels having an overall northeast outlet. This fluvial system formed probably under climatic conditions relatively drier than today's. During the early Pleistocene, there was pronounced erosion, followed by a renewed depositional phase ca. 40,000 14C yr B.P., with the development of prograding lobes and/or crevasse splays associated with a lake system (i.e., fan-delta) and/or fluvial flood plain areas. After a period of erosion, a fluvial system with eastward draining channels started to develop at around 27,000 14C yr B.P. The fluvial channels were overflooded in mid-Holocene time. This flooding is attributed to an increased period of humidity, with a peak between 5000 and 2500 14C yr B.P. The data presented herein support that, rather than being a monotonous area, the Amazonia was a place with frequent changes in landscape throughout the Neogene-Quaternary, probably as a result of climatic and tectonic factors. We hypothesize that these changes in the physical environment stressed the biota, resulting in speciation and thus had a great impact on modern biodiversity.