This work systematically investigates the orientation deviation effect on the elastoplastic deformation of a dual‐phase, nickel‐based single‐crystal superalloy through a combined experimental study and crystal plasticity finite element modelling method (CPFEM). Physically based, dual‐phase microstructural model was developed based on scanning electron microscopy (SEM), which was implemented by finite element (FE) modelling using a representative volume element (RVE) with periodic boundary conditions. An extended equivalent yield criterion coupled with CPFEM was adopted to describe the non‐uniform yield behavior induced by octahedral and cubic slip systems. The predicted results have shown that both the bulk behavior and localized stress–strain nature are orientation deviation dependent and that the first Euler angle plays a more important role in elastoplastic behavior than the second Euler angle. This study has thus advanced the basic understanding of the relationship between orientation deviation and the bulk deformation behavior of the dual‐phase nickel‐based single crystal.