The Tan-Lu Fault zone (TLFZ), often considered as a major sinistral strike-slip fault, extends in a NE to NNE direction for more than 2,000 km in eastern China. A structural analysis of the southern segment of the TLFZ (STLFZ) and surrounding areas enables us to propose the following evolution of this area during the Mesozoic-Palaeocene. The mid-Triassic NNW-SSE and late Triassic SSW-NNE to SSE-NNW strikes of the stretching lineations in the Zhangbaling massif favour ductile shears in a Zhangbaling metamorphic formation located along a ~NNE-SSW orientated “Tan-Lu margin”; this margin connected two margin segments situated north of the Dabie and Sulu belts. During the Mid-Late Triassic, the continental crust of the South China block (SCB) has been obliquely subducted along this margin below the North China block (NCB). We confirm that the SCB continental crust has been sliced and thrust toward the SSE and propose that the ductile thrusts have merged into the decollements of the sedimentary cover of the platform, forming the thrust-and-fold belt which has acted as a sinistral compressional transfer zone between the Dabie and Sulu collision belts. Thrusting and folding, under a N to NNE compression, affecting Jurassic deposits north and south of the Dabie Shan, indicate that the SCB/NCB collision has continued during the Jurassic. We show that a strike-slip tectonic regime occurred at that time, east of the STLFZ, which initiated as a sinistral continental transform fault between the Dabie and Sulu collisional belts. Dikes and strike-slip faults confirm that a ~NW-SE stretching was active during the basal early Cretaceous (~135–130 Ma), in and around metamorphic domes intruded by plutons. We show that strike-slip faulting, under a NW-SE compression-NE-SW tension, has been active subsequently, until the Aptian-? Early Albian (110/105 Ma), possibly until the Cenomanian (~95 Ma); at that time, the TLFZ has acted as a sinistral continental trans-current fault zone in eastern Asia. Subsequently, normal faulting, under a WNW-ESE extension, indicates that the TLFZ has been a normal fault zone during the Campanian-Palaeocene (~83–55 Ma), possibly until the Early Ypresian (~50 Ma). Sinistral offsets, in the order of several 100 of kilometres, on both sides of the TLFZ have been proposed; the present study does not support such large offset magnitudes.