This paper reviews previous knitting techniques for shoe uppers and identifies a common limitation in traditional and current footwear manufacturing methods: the unavoidable need for cutting processes. To address this issue, a novel three-dimensional (3D) fully fashioned knitting technology is proposed. By selecting different fabric structures and yarn combinations, 13 types of fabrics were designed and knitted using the Shima Seiki four needle-bed computer-controlled flat knitting machine. These fabrics were then subjected to mechanical and comfort performance tests to meet the functional zoning requirements of the new 3D shoe structure. The study investigated the effects of fabric structure and yarn combinations on fabric performance, including tensile strength, tear strength, bursting strength, abrasion resistance, breathability, and moisture permeability. Finally, a comprehensive analysis and evaluation of the test results for each fabric was conducted using SPSS software and grey relational analysis (GRA). The results indicated that Fabric A1 exhibited the best overall performance. The performance of the fabrics was influenced by both the structure and the combination of yarns, with the structural effect being more significant. Structures A and B, along with high-strength polyester filament yarns, demonstrated superior mechanical properties, while structures C and D showed better comfort performance. This research provides the optimal selection of fabric structures and yarn combinations for different areas of the shoe body. Finally, the study offers theoretical insights into the influence of structure and yarn combinations on fabric performance, contributing valuable knowledge to the design of fully fashioned 3D knitted footwear.