The effects of reduction in height per pass, roll diameter, and friction coefficient on the homogeneity of mechanical properties and shape change in flat-rolled twinning-induced plasticity steel wire were investigated. The goal was to improve the homogeneity of mechanical properties of a wire with area during flat rolling process using a numerical simulation, a hardness test, and electron backscatter diffraction techniques. Reduction in height per pass and roll diameter had large influences on both strain inhomogeneity and lateral spread of flat-rolled wire. Strain inhomogeneity and lateral spread increased with increasing the reduction in height per pass and roll diameter due to the higher length of the contact area. The underlying mechanism for the strain inhomogeneity and lateral spread of flat-rolled wire was highly related to the length of contact area. Hence, the length of the contact area needed reduction through controlling process conditions to improve the strain homogeneity of the flat-rolled wire. The effect of friction coefficient on lateral spread was negligible, whereas strain inhomogeneity slightly increased with friction coefficient. The combination of high and low reduction in height per pass with a smaller roll diameter improved the homogeneity of mechanical properties and microstructure over the area of the flat-rolled wire. Based on the results of numerical simulation and experimental test, a new practical strategy is proposed to achieve greater homogeneity of mechanical properties over the area of flat-rolled wire, which could be of great applicability in industrial fields.