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During the mass production of silica-based optical fibers, a large fiber preform is softened in a high-temperature furnace and is drawn to a small fiber with a diameter of about 125 μm. The hot fiber exiting the furnace is cooled rapidly by the surrounding air or by blowing a gas, and is subsequently coated with a polymer layer to provide a protection of the fiber surface. The overall quality of the fiber depends on the uniformity of the coating layer, which is strongly influenced by the manufacturing conditions. While the average thickness of the coating layer is extensively investigated in the literature, the studies on the coating thickness fluctuation lack a sound fundamental basis. In this paper, a linear perturbation analysis is adopted to predict the coating thickness variation under different processing conditions. An experimental correlation is developed to determine the initial amplitude of the thickness disturbance. Numerical results are presented for the first time to directly link the processing and geometric parameters with the coating thickness fluctuation in the final product. The results provide guidelines for selecting coating materials, system designs, and processing parameters to achieve uniform fiber coating layers.