The split-sleeve cold expansion technology is widely used in the aerospace industry, particularly for fastening holes, to enhance the fatigue life of components. However, to ensure proper assembly and improve surface integrity, reaming of the cold-expanded holes is necessary. This study investigates the effects of cold expansion and reaming processes on the fatigue performance of 7050-T7451 aluminum alloy. Fatigue tests, residual stress measurements, and microstructural analyses of the hole edges were conducted on specimens with four different hole diameters after cold expansion and reaming. It was found that the depth of reaming significantly affects fatigue life. During the cold expansion process, the compressive residual stress formed around the hole effectively improves fatigue performance. The experiments demonstrated that reaming by 0.2 mm to 0.4 mm helps eliminate minor defects, thereby improving fatigue life. However, reaming beyond 0.5 mm may lead to stress relief and the removal of dense grains at the hole edges, reducing fatigue life. Therefore, determining the optimal reaming size is crucial for enhancing the reliability of aerospace fasteners.