The four major Cenozoic tectonic phases in the Sierra de Perijá and adjacent basins are the early Eocene tectonic phase, the middle Eocene Caribbean orogeny, the late Oligocene phase, and the late Miocene to present Andean orogeny. Ages of unconformities associated with particularly rapid regional uplift during these phases are early Eocene (53 m.y.), middle Eocene (45 m.y.), late Oligocene (25 m.y.), and Pliocene (3 m.y.). Northwest-southeast compression may have commenced in the Perijá and the Maracaibo Basin as early as the early Eocene. By the middle Eocene the Macoa-Totumo arch had begun to form during intense alpine-type folding and thrusting to the east in Falcón and Lara. During the late Oligocene phase, the Palmar area was uplifted and the most important structural features for hydrocarbon accumulation in the Maracaibo Basin developed. The late Oligocene phase initiated a basement block tectonic style that culminated during the Pliocene in the northwest thrusting of the Santa Marta massif, Sierra de Perijá, and Venezuelan Andes over the adjacent basins. The main uplift of the Sierra de Perijá occurred during the late Miocene-Pliocene Andean orogeny. Right-lateral oblique-slip movement of 90 to 100 km on the Oca fault and left-lateral oblique-slip movement of 100 km on the Santa Marta fault were caused by late Tertiary overthrusting in the Sierra de Perijá and Santa Marta massif. The northwest-southeast shortening that uplifted the Santa Marta massif, Sierra de Perijá, and Venezuelan Andes is related to Caribbean-North Andean convergence along the South Caribbean marginal fault.

During the Pliocene the Panama volcanic arc collided with South America. The North Andean block became detached from the South American plate and is being wedged slowly to the north between the rapidly converging Nazca, Caribbean, and South American plates. The convergence of the three plates has produced rapid subduction at the Colombia trench (6.4 ± 0.7 cm/yr; 088° ± 7°), slow subduction at the South Caribbean marginal fault (1.7 ± 0.7 cm/yr; 128° ± 24°), and right-lateral shear (1.0 ± 0.2 cm/yr; 235° ± 5°) on the Boconó and East Andean fault systems.