Wear can occur in flat die pelletizers, often reducing service life. This study explores the issue of die hole wear in the pelletizing process of a standard Total Mixed Ration (TMR) feed. The selected TMR formulation comprises varying proportions of corn, alfalfa hay, and quinoa. A coupled DEM-FEM analysis was used to examine stress–strain conditions in various die hole regions at different material ratios, predict the fatigue life of flat die materials in the pelletizing process, and validate the accuracy of investigating flat die wear through friction wear tests. It was found that the entrance of the die hole experiences the most severe conditions in terms of equivalent stress and elastic strain. The fatigue life is shortest at the entrance, with a maximum equivalent stress of 42.8 MPa, a maximum equivalent elastic strain of 2.5 × 10−3, and a minimum fatigue life stress cycle of 5.0 × 105. In contrast, the equivalent stress and equivalent elastic strain at the middle and upper parts of the die hole are minimal, with an equivalent stress of 4.8 MPa and a minimum equivalent elastic strain of 2.8 × 10−4. Material wear tests revealed that the most severe wear on the flat die specimen occurred when the ratio of corn, alfalfa hay, and quinoa straw was 7:2:1, consistent with the findings from the DEM-FEM coupling method. The pelleting process, arising from the contact between the material and metal, encompasses adhesive wear, abrasive wear, and fatigue wear.