The quaternized polysulfone/polyquaternium-10 (QPSU/PQ-10) anion exchange membranes (AEMs) with a semi-interpenetrating network are prepared by the simple solution casting method. The effects of the mass ratio of chloromethylated polysulfone (CMPSU) to PQ-10 and the molar ratio of quaternized chloromethyl (QCM) to cross-linked chloromethyl (CCM) on the performance of AEM are systematically investigated. The results show that the introduction of PQ-10 endows the QPSU/PQ-10 AEM with excellent mechanical performance. More specifically, the QPSU/PQ-10 AEM has moderate water uptake, swelling ratio, and ion exchange capacity (IEC) at an appropriate composition ratio and crosslinking degree. In particular, the tensile strength and elongation at break of the QP0.5-1 membrane with the optimal composition ratio and crosslinking degree are 23.63 MPa and 20.07%, respectively; and its ion conductivity is up to 69.91 mS cm −1 at 80 °C. Furthermore, the peak power density of the single fuel cell assembled from the QP0.5-1 membrane is 75.64 mW cm −2 at 60 °C. Herein, the QPSU/PQ-10 AEM has good thermal oxidation stability, mechanical properties, and ion conductivity, highlighting the potential of bio-based PQ-10 as an ion-conducting functional molecule in AEMs.