The present study successfully designed a novel metastable β titanium alloy, Ti–8.8Cr–1.9Sn, exhibiting exceptionally high strain-hardening rate (∼2.4 GPa) as well as significant total elongation (∼48.2 %). Detailed analysis of the microstructure revealed that the successive activation of primary mechanical twins and primary SIM α" within β phases, along with secondary mechanical twins and secondary SIM α" within twinning zones during deformation, which results in a highly intricate network of deformation microstructures. Meanwhile, during deformation the microstructure undergoes dynamic refinement through the continuous occurrence of mechanical twinning and phase transformations, leading to a reduction in dislocation mean free path, thereby enhancing the strain-hardening rate. Importantly, the microstructural heterogeneity is formed due to generation of numerous heterogeneous interfaces, including β/α'', β/twin, α''/twin as well as twin/twinnano, thereby inducing additional HDI hardening resulting from the formation of GNDs for accommodating strain gradients near these interfaces. Furthermore, the relative mobile dislocation density ρm/ρm0 is significantly high during deformation, due to a reduced exhaustion rate and a high nucleation rate of mobile dislocations. The values of activation volume Va and V∗ typically range from 1b3–100b3, indicating the occurrence of cross-slip and dislocation nucleation. The interaction and accumulation between GNDs and mobile dislocations further contribute to the improvement of strain hardening rate. Therefore, the synergistic interaction activities of multiple deformation mechanisms lead to enhanced strain-hardening rate along with the large plasticity.