The South Tibetan Detachment System (STDS) marks a major decoupling horizon in the Himalaya, separating the highly metamorphosed infrastructure in the footwall from the weakly to unmetamorphosed superstructure in the hanging wall. The STDS stretches the entire range and is likely one of the most significant deformational features of the orogen, but its spatial and temporal evolution remain relatively unconstrained. As its name suggests, the STDS is a system of faults which occur at slightly different structural levels and are often diachronous. Detailed studies on the different strands are needed to understand the slip history of the system as a whole, which in turn will improve understanding of Himalayan orogenesis, thus informing tectonic models for continental orogenesis in general. I focus on some of the best exposed strands of the STDS which are located in the Annapurna region of Nepal. Outcrops within the shear zones of basal structures in the Kali Gandaki and Marsyandi valleys – the Annapurna and Chame detachments – contain leucogranites that are variably deformed via ductile slip on the detachments. I used U/Pb zircon and Th/Pb monazite geochronology to constrain emplacement ages of these leucogranites, which suggest ductile slip ceased prior to 14.95 ± 0.78 Ma and 16.0 ± 1.1 Ma on the Annapurna and Chame detachments respectively. 40Ar/ 39Ar muscovite and biotite, (U-Th)/He zircon and apatite thermochronology data and resulting thermal-kinematic models for samples I collected in the shear zones and footwalls of these detachments suggest further slip was ongoing on both detachments until ca. 12 Ma, although the majority of slip on the Chame detachment likely ceased by ca. 15-14 Ma. I also collected samples in the footwall of a structurally higher detachment in the Marsyandi and the resulting cooling ages and thermal-kinematic models suggest slip was contemporaneous with that on the lower Chame detachment. The new constraints on N-S extension on the STDS in the Annapurna region presented in this dissertation call into question the popular idea of a geodynamic change from N-S to E-W extension in the central Himalaya during the early Miocene, and emphasize the importance of the STDS as a major decoupling horizon.