Abstract: Wheat is one of the most vital staple crops in the world. Its milling process is one type of physical operation using extrusion-induced fragmentation. This study aims to explore the influence of the kernel morphological structure on its mechanical behavior under compressive loads using X-ray micro-computed tomography (micro-CT) modeling and finite element analysis (FEA). The research subjects were selected as wheat kernels with a moisture content of 16%. Accurate three-dimensional (3D) models were constructed for the simulation. The milling parameters were optimized for highly precise and low-loss wheat processing. A texture analyzer was employed to capture the stress-strain curves of the wheat kernels. Different morphological types were utilized under the ventral and lateral compression modes. These curves were used to determine the relationships among kernel morphology, elastic modulus, compressive strength, and ultimate load. The results show that the minimum elastic modulus and compressive strength were calculated as 35.15 and 5.57 MPa, respectively in the largest kernel type (A1). Large-grained wheat also exhibited a higher limit load during extrusion, indicating a stronger resistance to deformation. In contrast, the small-grained wheat shared the lower limit load more prone to rupture under relatively lower loads. Furthermore, the ultimate load reached 59.62 N under ventral compression, which was significantly higher than the 50.44 N observed under lateral compression. Therefore, the minimum extrusion load of 59.62 N was recommended for the full fragmentation of the wheat kernel in industrial milling. Three-dimensional geometric models of the wheat kernels were reconstructed using micro-CT scan data and reverse engineering techniques. Subsequently, the optimal models were imported into the FEA software. The distribution of the stress and strain fields was then simulated to clarify the total deformation behavior under compression. Simulation results indicated that the ventral groove region exhibited the most significant concentration of stress and strain, indicating the primary structural vulnerability during loading. In contrast, the equatorial plane was identified as the key governing region for the propagation of deformation throughout the kernel. Furthermore, the crack propagation paths in micro-CT images demonstrated that the high degree of spatial consistency with the high-stress regions was predicted by FEA simulation. In the ventral and lateral compression modes, the cracks were consistently extended inward along the longitudinal axis of the ventral groove. The initiation and propagation areas of these cracks closely matched the simulated regions of the maximum stress concentration. The high alignment between experimental observations and simulation validated the reliability and effectiveness of the model with micro-CT imaging. The mechanical behavior of the wheat kernels was also obtained to integrate the micro-CT imaging and FEA simulation. A robust model was also provided to accurately simulate the internal stress. The deformation mechanisms of wheat kernels under compression offered valuable theoretical insights for the milling industry. The grain morphology was highlighted to determine the structural role of the ventral groove and equatorial plane, particularly the mechanical response of the kernels. Such insights were crucial to refine the milling strategies, in order to minimize the structural damage for the high yield and nutritional integrity. Ultimately, the findings can greatly contribute to the theoretical models and engineering design for the optimal parameters of wheat milling. The key areas of the stress concentration were identified as the mechanical response of the kernels under various loading. The finding can also provide the scientific foundation to improve the milling efficiency, energy saving, and nutritional quality of wheat products.