The dynamic mass loss of ice sheets due to ice flow constitutes one of the biggest uncertainties in projections of ice-sheet evolution and sea-level rise. One central, understudied aspect of ice flow is how the bulk orientation of the ice-crystal lattice (fabric) translates to the mechanical anisotropy of ice. Here, we present a comprehensive analysis of the depth-averaged fabric distribution and corresponding directional flow enhancement factors covering a large area of the Northeast Greenland Ice Stream onset region. Our results are based on a combination of methods applied to extensive airborne and ground-based radar surveys, ice-core observations, and numerical ice-flow modelling. They show a strong spatial variability of the horizontal fabric anisotropy and a rapid crystal reorganization on the order of hundreds of years coinciding with the ice-stream geometry. The ice in parts of the ice stream is found to be up to one order of magnitude harder for pure-shear deformation in flow direction compared to isotropic ice, while the shear margins are potentially softened for horizontal simple shear by a factor of two. The high spatial resolution and large-scale coverage of our results is unprecedented and significantly contributes towards more accurate ice-flow models and a better understanding of ice-stream dynamics. Moreover, our estimated time scale of crystal reorganization and methodological approaches can potentially also be transferred to the investigation of ice on extraterrestrial bodies and other geologic materials.