Objective To make biomechanical evaluation on three prosthesis retention schemes for unilateral maxillary defects-clasp retention, one or two zygomatic implants and zygomatic implant and clasp united retention. Methods A three-dimensional (3D) finite element model of normal human skull was constructed based on CT scan data. The maxillary complex stress distributions on three reconstructed models were calculated and analyzed by 3D finite element method to make comprehensive comparison on stress level of the prosthesis, abutment, clasp, implants and zygoma. Results For single clasp retention, peak stress of the abutment was 130.7 MPa, and displacement of the prosthesis was 4.439 mm, while peak stress of the clap was 452.4 MPa, and stress of the contralateral orbital rim was 23.32 MPa. After one zygoma was implanted, the stress of the clap was reduced to 118.1 MPa, while peak stress of the abutment was 31.12 MPa, and stress of the contralateral orbital rim was only 5.387 MPa. For two zygomatic implant retention, zygomatic stress was decreased from 66.11 MPa to 48.12 MPa, and the maximum stress on the zygomatic implants was reduced from 500.2 MPa to 313.8 MPa. Conclusions For zygomatic implant and clasp united retention, the maxillofacial skeleton stress distributions were more consistent with the rules of bite force transduction. The research findings will provide important references for design and optimization of human unilateral maxillary defect reconstruction program.