Fatigue crack propagation behaviour of a novel TiZr-based alloy with two different microstructures was studied at room temperature. The measurements at increasing stress intensity factor range were conducted with loading ratios of 0.1 and 0.6. Based on the measurements, it is found that the alloy with the lamellar microstructure shows fatigue striations and secondary cracks. As to the equiaxed microstructure, many facets are generated instead of striations. Compared with the two cases, the alloy with the lamellar structure exhibits a better resistance to fatigue crack propagation, and the resistance increases with a decrease of stress ratio for both microstructures. Combined with electron backscatter diffraction analysis, the lower crack propagation rate of the lamellar microstructure can be ascribed to crack bifurcation and striation growth.