Methanol is a promising alternative fuel for heavy-duty engines due to its high-octane number and favorable combustion characteristics. However, optimizing combustion chamber designs for methanol engines to enhance performance and reduce knock tendency remains underexplored. This study investigates the effects of five typical combustion chamber shapes-reentrant, cylindrical, bathtub, hemispherical, and star-shaped-on the combustion characteristics, knock tendency, in-cylinder flow, and thermal efficiency of a heavy-duty spark-ignited methanol engine with exhaust gas recirculation (EGR). The results show that the improvement of the turbulent kinetic energy by increasing the tumble is higher than that by breaking the swirl, and accelerating the flame propagation speed to the side of the exhaust valve is an effective means of suppressing the knock. The hemispherical combustion chamber significantly improves in-cylinder turbulence, resulting in a 24.5% increase in turbulent kinetic energy in comparison to the traditional bathtub design. Furthermore, this chamber design exhibits a notable reduction in knock tendency during the later stages of combustion, attributable to the accumulation of the unburned mixture near the intake valve. Compared to the original bathtub combustion chamber, the indicated thermal efficiency of the hemispherical combustion chamber increased by 0.8%, with the effective thermal efficiency estimated to reach 42.4% based on the mechanical efficiency obtained from the bench test. In conclusion, the hemispherical combustion chamber is the most optimal option among the five designs. The findings presented herein offer a novel approach to optimizing combustion chambers for methanol engines and providing a path to improved engine performance and efficiency.