Additive manufacturing provides a novel and robust way to prepare medical product with anatomic matched geometry and tailored mechanical performance. In this study, the surface characteristics, microstructure, and mechanical properties of fused deposition modeling (FDM) prepared polyether-ether-ketone (PEEK) were systematically studied. During the FDM process, the crystal unit cell and thermal attribute of PEEK material remained unchanged, whereas the surface layer generally became more hydrophilic with an obvious reduction in surface hardness. Raster angle has a significant effect on the mechanical strength but not on the failure mechanism. In practice, FDM fabricated PEEK acted more like a laminate rather than a unified structure. Its main failure mechanism was correlated to the internal voids. The results show that horizontal infill orientation with 30° raster angle is promising for a better comprehensive mechanical performance, and the corresponding tensile, flexural, and shear strengths are (76.5 ± 1.4) MPa, (149.7 ± 3.0) MPa, and (55.5 ± 1.8) MPa, respectively. The findings of this study provide guidelines for FDM-PEEK to enable its realization in applications such as orthopedic implants.