High-speed spindles often suffer from degeneration in its machining accuracy caused by the uneven distribution of temperature field. In order to improve the machining accuracy of high-speed spindles, a three-dimensional (3D) finite element analysis (FEA) model, which considered the combined effect of thermal contact resistance (TCR) and the change in heat power and stiffness caused by thermal displacements of bearing components on the accuracy of simulation results, was proposed to conduct transient thermal-structure analysis of high-speed spindles. The predictive model for TCR was proposed based on the fractal theory to characterize the rough surface morphology with disorder, self-affinity and non-stationary random features. And a contact mechanics model was developed to consider the influence of asperities’ deformation on TCR. The thermal-structure model of bearing was proposed to calculate the heat power and stiffness based on the quasi-static mechanics analysis. The FEA model proposed in this paper was used to simulate the temperature field distribution and thermal deformations of the high-speed spindle system. Then thermal characteristic experiments were conducted to validate the effectiveness of this model. The results showed that the FEA model was much more accurate than the traditional model which ignored the above two important factors. The temperature field and thermal errors of the spindle system were analyzed.