Rotating machinery often encounters excessive vibration due to various excitation sources. Among others, the synchronous excitation due to rotating unbalance and initial deformation is acknowledged to be one of the major sources of vibration in rotor-bearing systems. In this paper, a synchronous response analysis method in the presence of the initial deformation is proposed to investigate the peculiar effect of the initial deformation on the response of general flexible rotor-bearing systems with rotational speed dependency and the anisotropy. Experiments are performed and compared with computational results to verify the proposed analysis method. Two numerical examples are also provided to illustrate the characteristics of the synchronous response of general rotor-bearing systems due to the initial deformation.