We trace source variations of active margin granitoids which crystallised intermittently over ~300 Ma in varying kinematic regimes, by combining zircon Lu-Hf isotopic data from Early Palaeozoic to Early Jurassic igneous and metaigneous rocks in the Mérida Andes, Venezuela and the Santander Massif, Colombia, with new whole rock Rb/Sr and Sm-Nd isotopic data, and quartz O isotopic data. These new data are unique in South America because they were obtained from discrete magmatic and metamorphic zircon populations, providing a high temporal res- olution dataset, and compare several isotopic systems on the same samples. Collectively, these data provide valu- able insight into the evolution of the isotopic structure of the continental crust in long-lived active margins. Phanerozoic active margin-related granitoids in the Mérida Andes and the Santander Massif yield zircon Lu-Hf model ages ranging between 0.77 Ga and 1.57 Ga which clearly define temporal trends that can be correlated with changes in tectonic regimes. The oldest Lu-Hf model ages of N1.3 Ga are restricted to granitoids which formed during Barrovian metamorphism and crustal thickening between ~499 Ma and ~473 Ma. These granitoids yield high initial 87Sr/86Sr ratios, suggesting that evolved, Rb-rich middle to upper crust was the major source of melt. Granitoids and rhyolites which crystallised during subsequent extension between ~472 Ma and ~452 Ma yield younger Lu-Hf model ages of 0.80 Ga–1.3 Ga and low initial 87Sr/86Sr ratios, suggesting that they were de- rived from much more juvenile, Rb-poor sources such as mafic lower crust and mantle-derived melts. The rapid change in magmatic sources at ~472 Ma can be attributed either to reduced crustal assimilation during extension, or a short pulse of crustal growth by addition of juvenile material to the continental crust. Between ~472 Ma and ~196 Ma Lu-Hf model ages remain mostly constant between ~1.0 and ~1.2 Ga. The large scatter and the absence of definite trends in initial 87Sr/86Sr ratios suggest that both mafic, Rb-poor, and evolved Rb-rich sources were im- portant precursors of active margin magmas in Colombia and Venezuela throughout the Palaeozoic to the Early Jurassic. Previous studies have shown that the genesis of arc magmas may be stimulated by heat advection to the crust during the underplating of mantle derived melt, but the absence of permanent younging trends in Lu-Hf model ages from ~472 Ma to ~196 Ma suggests that very little new crust was generated during this period in the studied region. An overwhelming majority of the analysed igneous rocks yield zircon Lu-Hf model ages of N1 Ga which may be accounted for by documented local crustal end members of 1 Ga–1.6 Ga, and do not require contributions from the depleted mantle. Therefore, recycling of ~1 Ga and older crust was a dominant process in the north-western corner of Gondwana between ~472 Ma and ~196 Ma. This study shows that whole rock Sm-Nd and zircon Lu-Hf data can be interpreted similarly regarding the age of the source regions, whereas Rb-Sr and O isotope data from the same rocks yield valuable information regarding the geochemical nature of the source.