This study aimed to optimize the process parameters for the ultrasonic spraying of a nanooptical film coating on a large-area glass substrate, using the Taguchi experimental design. The key process parameters affecting spraying performance include the speed of the spray nozzle, flow rate of spray solution, airflow strength, spray height, and spray distance. The Taguchi quality characteristic used was the uniformity of light transmittance. With a glass substrate area of 52 cm2, the optimal process parameters for uniform spraying of silica solution were obtained via the Taguchi design method. The experiments confirmed that the optimal process parameters could effectively improve the uniformity of visible light transmittance; the S/N ratio of optical transmittance uniformity rose by approximately 2.79, transmittance reached 92.02%, and the transmittance uniformity was controllable to within 0.12%.