The Cerro Uyarani Metamorphic Complex (CUMC) in Bolivia provides a record of complex Paleoproterozoic to Mesoproterozoic tectono-magmatic evolution, as revealed through U–Pb isotopic analysis of zircon from three litho-domains (DI – DIII). The Paleoproterozoic crystalline basement was subject to two stages of Mesoproterozoic reworking. This detailed study of zircon textures and geochronology, including determination of first Hf-isotope data, from felsic granulites, banded granulites and amphibolites reveals a first Paleoproterozoic event at 1.81–1.74 Ga in magmatic and some metamorphic zircon cores, with zircon ϵHfT values of +6.3 to −0.2. A subsequent Mesoproterozoic event can be divided into 2 cycles: a first one at 1.19–1.17 Ga is reflected by recrystallized rims and cores of zircon with ϵHfT values of −6.8 to −3.6. This cycle is here associated with migmatization of the basement, during which the Paleoproterozoic crust was differentiated into DI-leucosome rich migmatite, DII-leucosome rich migmatite, DIII – our best proxy of Paleoproterozoic crust, melanosome, and paleosome. The second cycle at ∼1.1–1.0 Ga is recorded in metamorphic rims and by newly grown metamorphic zircon with ϵHfT values of −15.1 to −2.6. This event was responsible for the transformation of the CUMC migmatitic basement into granulite facies rocks. We interpret that the CUMC was part of the southernmost portion of the Arequipa terrane from, at least, ∼1.74 Ga and that it then became attached to the Paraguá terrane and Amazon craton at 1.19–1.17 Ga. This collision generated migmatites, and then, with the arrival of Laurentia passing through the Arequipa terrane front (with CUMC at the Arequipa terrane), the conditions of metamorphism were raised to granulite facies. A younger event of lower metamorphic grade and likely associated with fluid-driven alteration is recognized in the partial retrograde transformation of mafic granulites into amphibolites. Our new U–Pb and εHfT data indicate that the Paleo-to Mesoproterozoic history of the CUMC is, thus, similar to that of the Arequipa terrane, Rio Apa terrane, the SW Amazon craton, and other Grenville-age inliers; but it was distinct from the evolution of the Sierra de Maz and Pie de Palo of the hypothetical MARA craton.