This study investigates seismic wave amplification effects in the Indo-Gangetic (IG) basin for possible large earthquakes in the region using spectral-element simulations. The Indo-Gangetic basin is a large and deep sedimentary basin that covers the northern part of India, in which several mega-cities are located, including the capital city of New Delhi. The seismicity in the region due to presence of many active tectonic faults is an important matter of concern for engineers. The damage caused in a future large earthquake could affect a huge population and hinder the development of numerous large-scale industrial establishments. Due to local soil conditions and the structural complexity of the sedimentary basin, seismic wave amplification is expected. However, the absence of seismic data for large earthquakes and limited knowledge of the structure of the basin poses challenge in estimating shaking amplifications. Therefore, we model the 3D structure of the basin using Spectral Finite Element method (Specfem3D) including the topography of the Himalayan mountains, and compute synthetic seismograms for a suite of simulated rupture scenarios. First, we use two past earthquakes in the basin to calibrate our 3D model by comparing the simulated ground motions with the recorded data. Later, we consider realizations of potential future large earthquake (Mw 7.1), by generating different kinematic rupture models. We simulate earthquake scenarios for different source parameters to quantify the statistics of expected ground shaking levels. We then infer seismic wave amplification as a function of both frequency and basin depth for complex seismic sources. Our results indicate a maximum amplification of 16 in Peak Ground Velocity (PGV) and 19–35 in Spectral Accelerations (Sa) at long periods. The results presented in this study may be useful for engineers to predict ground motions for future large earthquakes in absence of any available seismicity data.