Granite plutons and small stocks of similar Late Neoproterozoic age are widespread in the southernmost section of the Dom Feliciano Belt of Uruguay on both sides of the Sierra Ballena Shear Zone (SBSZ): Nico Pérez Terrane (e.g. western domain) and Punta del Este Terrane (e.g. eastern domain). Most granites exposed at both sides of the SBSZ largely show a field paucity of associated mafic rocks and similar characteristics to those derived from the partial melting of I-type metaigneous sources. However, granites with signatures akin to S- and A-type sources do also occur. Western domain granites display crystallization ages between 596 and 610 Ma, Archaean to Neoproterozoic inheritance ages (3072–640 Ma) and strongly evolved isotopic signatures (87Sr/86Sri of 0.708352; εNd of −14 to −20; Nd TDM2 ages of 2.3–2.8 Ga; εHf(t) of −21 to −27 and zircon Hf model ages as old as 3.6 Ga). Granites from the eastern domain, while showing similar but slightly broader range of crystallization ages (567–617 Ma), reveal contrastingly younger inheritance (775–589 Ma) and less evolved isotope characteristics (87Sr/86Sri of 0.707959–0.711420; εNd of −2.0 to −7.7, Nd TDM2 of 1.4–1.8 Ga; εHf(t) of −4.2 to −9.2 and zircon Hf model ages as old as 2.1 Ga). Combined field evidence and the contrast in ages of inherited zircon populations and in zircon and whole-rock isotopic geochemical compositions indicate that granites were generated by the reworking of old crustal blocks of different ages. Granitic melts were produced from partial melting of metaigneous and metasedimentary sources at lower to intermediate crustal levels with a possible contribution of a minor mantle component. A regional geological and isotopic resemblance between different geographic sections of the Pan-African/Brasiliano orogenic belts of Brazil and Uruguay might be significant and indicative of a certain commonality of sources in the production of granitic melts on a regional scale.