Abstract The sedimentary basins of western Venezuela contain large volumes of oil. However, most of the large structures have already been produced. Exploration for new reserves of light and medium oil now depends on integrated studies that lead to a more comprehensive basin evaluation. This paper presents an integrated account of the Lake Maracaibo and Barinas-Apure basins of western Venezuela. It is a fully integrated study but focuses on the genetic and seismic stratigraphy of more than 600 wells, reference outcrops, and 4000 km of reflection seismic data. Six unconformity-bounded supersequences record the dynamics of Mesozoic-Cenozoic basin evolution from extension to collision. Supersequence A was deposited during an episode of Jurassic rifting, and supersequence B corresponds to the subsequent Early-Late Cretaceous passive margin. Supersequence C marks the transition to a compressive regime in the Late Cretaceous and early Paleocene. Compression resulted from collision and obduction of the Pacific volcanic arc with the South American plate. Supersequence D records the development of the late Paleocene-middle Eocene foreland basin in front of the volcanic arc and emplacement of the Lara nappes. Supersequences E and F are attributed to modification of the foreland basin by late Eocene-Pleistocene collision of the Panama arc. The uplifted Serranla de Perija, Macizo de Santander, and Mérida Andes partitioned the foreland basin, creating the present Lake Maracaibo and Barinas-Apure basins. Supersequence B contains the Cretaceous La Luna source rock (sequences K3, K4, K5). The Colon and Burgúita formations form the principal supersequence C seals (sequence K6). The principal reservoir units occur in supersequence D, including the prolific Eocene Misoa and Gobemador formations (sequences TI, T2). Reservoirs of the La Rosa and Lagunillas formations occur in supersequence F and in the Betijoque Molasse.