Laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) analyses of 29 samples from the Eastern Cordillera of Colombia reveal the origin of northern Andean basement and patterns of sedimentation during Paleozoic subsidence, Jurassic–Early Cretaceous extension, Late Cretaceous postrift subsidence, and Cenozoic shortening and foreland-basin evolution. U-Pb geochronological results indicate that presumed Precambrian basement is mainly a product of early Paleozoic magmatism (520–420 Ma) potentially linked to subduction and possible collision. Inherited zircons provide evidence for Mesoproterozoic tectonomagmatic events at 1200–1000 Ma during Grenville-age orogenesis. Detrital zircon U-Pb ages for Paleozoic strata show derivation from Andean basement, syndepositional magmatic sources (420–380 Ma), and distal sources of chiefly Mesoproterozoic basement (1650–900 Ma) in the Amazonian craton (Guyana shield) to the east or in possible continental terranes along the western margin of South America. Sedimentation during Jurassic–Early Cretaceous rifting is expressed in detrital zircon age spectra as Andean basement sources, recycled Paleozoic contributions, and igneous sources of Carboniferous–Permian (310–250 Ma) and Late Triassic–Early Jurassic (220–180 Ma) origin. Detrital zircon provenance during continued Cretaceous extension and postrift thermal subsidence recorded the elimination of Andean basement sources and increased influence of craton-derived drainage systems providing mainly Paleoproterozoic and Mesoproterozoic (2050–950 Ma) grains. By Eocene time, zircons from the Guyana shield (1850–1350 Ma) dominated the detrital signal in the easternmost Eastern Cordillera. In contrast, coeval Eocene deposits in the axial Eastern Cordillera contain Late Cretaceous–Paleocene (90–55 Ma), Jurassic (190–150 Ma), and limited Permian–Triassic (280–220 Ma) zircons recording initial uplift and exhumation of principally Mesozoic magmatic-arc rocks to the west in the Central Cordillera. Oligocene–Miocene sandstones of the proximal Llanos foreland basin document uplift-induced exhumation of the Eastern Cordillera fold-thrust belt and recycling of the Paleogene cover succession rich in both arc-derived detritus (dominantly 180–40 Ma) and shield-derived sediments (mostly 1850–950 Ma). Late Miocene–Pliocene erosion into the underlying Cretaceous section is evidenced by elimination of Mesozoic–Cenozoic zircons and increased proportions of 1650–900 Ma zircons emblematic of Cretaceous strata.