Details of lithospheric structures in three‐dimensions (3‐D) are key to understanding the dynamics of crustal deformation and earthquakes in active orogenic systems. In this study, we develop a 3‐D model of the eastern Tibetan Plateau using the Skua‐Gocad software based on the latest Rayleigh wave tomography. We perform a quantitative modeling workflow to map the details of the Moho discontinuities and the high‐velocity anomalies. Then, we integrate the topography, major active faults, large earthquakes, and crustal Poisson's ratios to analyze the relationship between the shallow and deep structures of this region. Our study shows that the Moho is generally coupled with the topography. A steep Moho ramp exists under the plateau margin and its surface projection intersects the Longmen Shan (LMS) at a low oblique angle (~22°). Active deformation and large earthquakes are related to the steep Moho ramp under the plateau margin. Moreover, based on a 3‐D model of the Poisson's ratio perturbations, we find that deformation across the central LMS is characterized as a crocodile‐type wedge in the crust and lithospheric mantle, due to the resistance of the Yangtze craton and isostatic rebound. We suggest that a tectonic wedging model that contains both the upper‐crust thrusting and lower‐crustal thickening contribute to the LMS orogeny. Three‐dimensional visualization of the lithospheric structure is well suited to reveal the different levels of deformation and their relationships. Quantitative modeling methods provide effective constraints on the active blocks in the eastern Tibetan Plateau.