The invention provides a milling and grinding method of a large-caliber off-axis aspherical lens. By designing a clamp device with an angle and putting the to-be-machined off-axis aspherical lens at the center of a machine tool rotating table in the manner that the to-be-machined off-axis aspherical lens inclines by a certain angle in the meridian direction of the off-axis aspherical lens, the rise change rate of the to-be-machined off-axis aspherical lens is decreased, and milling, grinding and coping forming continues to be conducted according to designed parameters of the off-axis aspherical lens on the basis that a blank of the to-be-machined off-axis aspherical lens is milled and ground to be the closest to a fitting spherical surface. By means of the method, the machining amount of the subsequent grinding stage is decreased, the machining stability and precision are improved, the milling and grinding period is shortened, and the machining efficiency is improved.