An off-axis three-mirror anastigmatic optical system with the offset apertures configuration as a typical unobscured optical system is frequently used in various optical instruments. The practical applications show that this type of system has a higher sensitivity in alignment. To reduce the alignment sensitivity of the unobscured optical systems, a desensitization design method with an adjustment-optimization-evaluation process is proposed. By ray path difference analysis based on the optical system mathematical models, the mirror off-axis magnitude value is determined as a significant factor influencing system alignment sensitivity. Accordingly, in the desensitization design process, the mirror off-axis magnitude value is set as an adjustment, and the image quality and system sensitivity are set as the criteria. By a design example, it proves that the desensitization design method is effective and practical, and the design result sensitivity analysis not only verifies that the off-axis magnitude is a significant factor that influences the system alignment sensitivity, but also finds that there is a positive correlation relation between system sensitivity and off-axis magnitude value. The desensitization method can design the unobscured optical systems with less alignment sensitivity and robust tolerance.