Eight different 3D weft-knitted fabrics, consisting of outer, binding, and inner layers, were designed and produced on E20 and E28 circular weft-knitting machines. First, in the outer layer, high molecular weight polyethylene multifilament yarns and steel wire (0.05 mm diameter), twisted with high molecular weight polyethylene multifilament yarns, were used because of their exceptional properties to resist the mechanical risks. Second, in the inner layer, hydrophobic polyester spun yarns were chosen for their suitability to be used in contact with skin. Finally, in the binding layer, synthetic elastic textured polyamide yarns were used to connect the outer and inner layers. Following the standard EN 388, diverse tests were conducted to determine the resistance of the developed 3D weft-knitted fabrics to mechanical risks, i.e., circular blade cut, puncture, abrasion, and tear. The analysis showed that the quantity of steel wire in knitted structure highly influences circular blade cut and abrasion resistance, and moderately influences tear resistance for all the investigated knitted fabrics. While a strong positive correlation between the quantity of steel wire and the puncture force was defined only for 3D fabrics knitted on an E20 circular weft-knitting machine. The findings of the research lead to the conclusion that the designed 3D weft-knitted fabric structures, where the outer layer ensures protection against mechanical risks, while the inner layer is designed for contact with skin, provide complex protection against diverse mechanical risks.