We develop a crystal plasticity model to investigate the coupled actions of crystal orientation, grain neighborhood and grain-to-grain elasto-plastic interactions on dynamic strain aging and the onset and development of associated plastic strain localization in Al-Li alloys. Considering simple model multilayered microstructures with preferred orientations representative of rolled alloys, the aim is to identify grain orientation couples that can limit dynamic strain aging induced strain localization without compromising the flow stress and strain hardeningproperties. To this end, a slip system-based formulation of dynamic strain aging is implemented in a crystal plasticity finite element framework. The model validity is first checked with the simulation of a tensile specimen loaded at quasi-static applied strain rate. The introduction of dynamic strain aging allows predicting complex propagation of intense plastic localization bands. We further investigate the influence of crystal orientations on early strainlocalization in Al-Cu-Li-Mg alloys, by performing simulations representative of the early stage of a Kahn Tear test for single crystals and layered polycrystals. Using experimentally reported crystal orientations for rolled microstructures, the simulation results show that in both single and multilayered crystals, there is a strong influence of dynamic strain aging on localization patterns, as well as a significant orientation dependence. In multilayered crystals, the nature of strain localization can be remarkably modified when stand-alone crystals of a certain orientation are coupled with other orientations: strain localization may intensify or fades away depending on the coupling with neighboring orientations.