The Main Himalayan Thrust (MHT), the most prominent tectonic boundary between the subducting Indian crust and the overthrusting Himalaya, occurs as a key structure dominating the active tectonics of the Himalaya. Previous studies indicate that the MHT forms a major buried ramp in the mid-crust, which with varying geometry and kinematics leads to a distinctive pattern of uplift along the Himalaya. However, it is unknown if and how these along-strike variations are correlated with the well-known active N-S-trending normal faults across the Himalaya and Tibetan Plateau. In this study, we report 39 new apatite and zircon fission track ages in the Cona area (~92°E) in the eastern Himalaya, coinciding with the easternmost N-S-trending extensional system in southern Tibet, the Cona Cross Structure (CCS). Spatial patterns of surface cooling ages are consistent with an overthrusting of the Himalayan wedge above a mid-crustal ramp in the MHT. Thermokinematic inverse modeling yields contrasting geometries and kinematics for the mid-crustal ramp on both sides of the CCS. Specifically, to the west of the CCS, the MHT developed a major ramp (with a dip angle of 20.4 ± 2.9°) spanning 50–70 km, which initiated at ~11.7 ± 0.6 Ma. To the east, thermokinematic inversion suggests a much less developed ramp spanning only ~10–15 km, initiated at ~6.8 ± 0.3 Ma. These results imply an ~14-km deeper depth of the MHT to the west of the CCS than to the east. Our modeling also suggests distinctive and evolving ramp-thrusting rates for the MHT on both sides of the CCS. This suggests an independent deformation accommodation by the MHT ramp thrusting in segments divided by the CCS along strike. Our study highlights a genetic correlation between the active orogenic-parallel ramp evolution and the N-S-trending faulting across the Himalaya, which divides the orogenic-parallel tectonics into independent structural segments.