Objective For patient-specific open-wedge high tibial osteotomy (OWHTO), a novel anatomical fixation plate was designed, and the effects of geometric parameters and material selection on biomechanical fixation were studied. Methods A patient-specific OWHTO anatomical fixation plate was designed and constructed, and the effects of design parameters (thickness, width, and length of the fixation plate) and four different materials (stainless steel, titanium alloy, magnesium alloy, and PEEK) on the biomechanics of the OWHTO fixation system were studied using finite element analysis. The biomechanical differences between the anatomical fixation plate and TomoFix fixation plate were also compared. Results The thickness had a greater effect on the micromotion of the osteotomy space than the length and width of the fixation plate did. Titanium alloy or magnesium alloy fixation plates were more conducive than stainless steel and PEEK materials in obtaining reasonable stability and mechanical transfer simultaneously. Compared with that of the TomoFix plate, the maximum von Mises stress of the anatomical fixation plate was reduced by 13.5%; the maximum von Mises stress of the screws and tibia was increased by 9.8% and 18.4%, respectively; and the micromotion at the maximum osteotomy space cc was increased by 49.3%. Conclusions Anatomical fixation plates have a positive effect on reducing the stress-shielding effect and improving biomechanical properties under the premise of ensuring stability. This study provides a reference for the development of OWHTO anatomical fixation plates.