In this paper, a comprehensive analytical model for the fatigue life prediction of ball bearing in various operating conditions is presented. Not only the internal clearance variations induced by the centrifugal expansion and assembly interference but also ball inertia forces and ball–raceway separations are fully considered in theoretical modeling to achieve accurate life prediction of the ball bearing. The model has been validated by comparison with the static results in previous literature. Based on this, the results of the load distribution and fatigue life versus the internal clearance of ball bearing under various operating conditions are studied. The results show that there is always an optimal clearance to maximize bearing fatigue life for the radial load or the combined load conditions, and the size of the optimal clearance for bearing life is determined by both the load conditions and rotating speeds to ensure the uniformity of the internal load distribution of the ball bearing. Therefore, the above-mentioned theoretical and conclusions can be used in structural design optimization and assembly parameters selection of ball bearing to maximize the life characteristic.