Crustal anatectites are frequently observed along ocean–continent active margins, although their origins are disputed with interpretations varying between rift-related and collisional. We report geochemical, isotopic and geochronological data that define an ~ 1500 km long belt of S-type meta-granites along the Andes of Colombia and Ecuador, which formed during 275–223 Ma. These are accompanied by amphibolitized tholeiitic basaltic dykes that yield concordant zircon U–Pb dates ranging between 240 and 223 Ma. A model is presented which places these rocks within a compressive Permian arc setting that existed during the amalgamation of westernmost Pangaea. Anatexis and mafic intrusion during 240–223 Ma are interpreted to have occurred during continental rifting, which culminated in the formation of oceanic crust and initiated the break-up of western Pangaea. Compression during 275–240 Ma generated small volumes of crustal melting. Rifting during 240–225 Ma was characterized by basaltic underplating, the intrusion of tholeiitic basalts and a peak in crustal melting. Tholeiitic intrusions during 225–216 Ma isotopically resemble depleted mantle and yield no evidence for contamination by continental crust, and we assign this period to the onset of continental drift. Dissected ophiolitic sequences in northern Colombia yield zircon U–Pb dates of 216 Ma. The Permo-Triassic margin of Ecuador and Colombia exhibits close temporal, faunal and geochemical similarities with various crustal blocks that form the basement to parts of Mexico, and thus these may represent the relict conjugate margin to NW Gondwana. The magmatic record of the early disassembly of Pangaea spans ~ 20 Ma (240–216 Ma), and the duration of rifting and rift–drift transition is similar to that documented in Cretaceous–Tertiary rift settings such as the West Iberia–Newfoundland conjugate margins, and the Taupo–Lau–Havre System, where rifting and continental disassembly also occurred over periods lasting ~ 20 Ma.