The occurrence of Permian magmatic rocks in the Colombian Andes is restricted to a few localities. Previous works have focused mainly on explaining its tectonic setting, whereas petrogenesis has received less attention. This study closes this gap by reporting whole‐rock geochemistry, zircon U–Pb geochronology, trace elements and Hf isotopes from massive and mylonitic granitoids along central Colombia to constrain their age, source and petrogenesis. Our results show that the granitoids have a calc‐alkaline character, are rich in light‐rare elements (LREEs) and large‐ion lithophile elements (LILEs), present negative Nb and Ti anomalies, crystallized between ca. 276–265 Ma and show variable εHf(i) values ranging from −1.5 to +1.7. Combining our results with published geochemical, geochronological and isotopic data from this region, we suggest that the Middle Permian granitoids from the Tolima region were formed in a continental magmatic arc installed at the western margin of Gondwana, where partial melting of the mantle wedge and further crustal assimilation of the magmas with an old radiogenic and heterogeneous crust were essential processes for the modification of the source of the magmas that generated the granitoids. The Middle Permian may have reached the peak magmatic conditions (ca. 280–270 Ma), according to the recurrence of ages in this time interval. This period of magmatic activity may have been interrupted by the Triassic extensional period related to the beginning of the Pangea breakup.