TC21 titanium alloy has been successfully used in the structural die forgings of aviation owing to its excellent damage tolerance. However, because of the difference in the equivalent strains of die forgings, the microstructure and properties of variable cross-sections are considerably different, affecting the service life of the structural parts. Therefore, the microstructure and mechanical properties of β-forged TC21 titanium alloy die forgings with variable cross-sections were characterized using Deform software simulation, OM, SEM, XRD, EBSD, and tensile and impact tests, and the primary factors affecting the tensile and impact properties as well as their anisotropy were comprehensively analyzed. The results showed that the overall shape of the die forgings was complex and the effective strain was concentrated in the range of 0.75-1.20. The evidence of the flow was obvious at high strain, the substructure increased, and the narrow cross-section led to a faster cooling rate. This resulted in the decrease of α_p content and refinement of α_s, which together led to the increase in strength. The evolution of various texture components under high strain during thermal deformation and heat treatment was analyzed, and finally the strong texture of residual β phase <110>//LD and {0002} weak texture of transformed α phase were formed. The strength anisotropy caused by the strong texture was analyzed from α phase slip system and β phase densely packed plane. The impact load-displacement curves showed that the impact energy was mainly consumed via the initiation energy. Combining with the prior β grain arrangement, the fracture modes of impact and tensile fracture in different orientations were discussed. Finally, a tensile fracture model was proposed, which explained the reason that there was a good strength and plastic matching at a high strain of 1.20. This work provides material research support for optimizing the uniformity design of TC21 alloy variable cross-section die forgings.