In order to better constrain the paleogeographic evolution of south China we measured Sm‐Nd and Rb‐Sr isotopic compositions for 23 Mesozoic granites that crop out throughout the area. Tightly grouped neodymium depleted mantle model ages (1.4 ± 0.3 Ga) suggest the region is underlain by relatively homogeneous Proterozoic crust and fail to define crustal provinces. Neither the isotopic nor geologic data suggest that a Mesozoic suture exists. However, granites possessing anomalously high Sm (>8 ppm) and Nd (>45 ppm) concentrations, relatively high initial epsilon neodymium (−4 to −8), and high but variable initial87Sr/86Sr (0.759 to 0.713) form a northeast trending zone that coincides with two prominent Mesozoic basins. Southeast of the zone lie the majority of Mesozoic intrusives and Upper Triassic to Lower Cretaceous extensional basins found in south China. Mesozoic paleomagnetic poles are well clustered northwest of the zone. Pre‐Cretaceous poles southeast of it are discordant with respect to those from the northwest. The only recognized tectonostratigraphic terrane in south China lies southeast of the zone. The terrane is bordered by a northeast trending sinistral fault that was active in the Mesozoic. Other faults in south China have similar attitudes, ages, and sense of shear. Together, the observations suggest that the Mesozoic tectonic regime in south China consisted of strike‐slip activity plus concomitant rifting as terranes or fragments of similar crust were transported north along sinistral faults. The zone, defined by the granites enriched in Nd and Sm, demarcates displaced terranes to the southeast from relatively stable land to the northwest.