Abstract: The evolution of the microstructure and mechanical properties of WE43 magnesium alloy during multipass hot rolling was investigated. Results revealed that multipass hot rolling promoted the formation of small second phases, which was conducive to multiple dynamic recrystallization, consequently improving the microstructure homogeneity and refining the average grain size from 34.3 μm in the initial material to 8.83 μm. Meanwhile, the rolling deformation rotated abundant c-axis of the grains in the normal direction, resulting in a strong fiber texture. The yield strength in the rolling direction (RD) was improved from 164 MPa in the initial material to 324 MPa in the Pass 3 sheet due to fine-grained strengthening, second-phase strengthening, and texture modification. In addition, the distribution maps of the deformation mechanism indicated that the yield strength anisotropy between the RD and the transverse direction (TD) can be attributed to the effects of the texture component on the dominant mechanism. The dominant deformation mechanism during the tensile test was the prismatic slip caused by the strong basal texture of the RD, whereas it had a lesser proportion of prismatic slip under the influence of the weak basal texture of the TD. Compared to the basal slip, the higher critical resolved shear stress of the prismatic slip resulted in a higher increase in yield strength along the RD at approximately 51 MPa than that along the TD (RD: increase of 160 MPa; TD: increase of 109 MPa).