Metastable β titanium alloys possess excellent strain-hardening capability, but suffer from a low yield strength. As a result, numerous attempts have been made to strengthen this important structural material in the last decade. Here, we explore the contributions of grain refinement and interstitial additions in raising the yield strength of a Ti-12Mo (wt.%) metastable β titanium alloy. Surprisingly, rather than strengthening the material, grain refinement actually lowers the ultimate tensile strength in this alloy. This unexpected and anomalous behavior is attributed to a significant enhancement in strain-induced α’’ martensite phase transformation, where in-situ synchrotron X-ray diffraction analysis reveals that this phase is much softer than the parent β phase. Instead, a combination of both oxygen addition and grain refinement is found to realize an unprecedented strength-ductility synergy in a Ti-12Mo-0.3O (wt.%) alloy. The advantageous effect of oxygen solutes in this ternary alloy is twofold. Firstly, solute oxygen largely suppresses strain-induced transformation to the α’’ martensite phase, even in a fine-grained microstructure, thus avoiding the softening effect of excessive amounts of α’’ martensite. Secondly, oxygen solutes readily segregate to twin boundaries, as revealed by atom probe tomography. This restricts the growth of {332} deformation twins, thereby promoting more extensive twin nucleation, leading to enhanced microstructural refinement. The insights from our work provide a cost-effective rationale for the design of strong yet tough metastable β titanium alloys, with significant implications for more widespread use of this high strength-to-weight structural material. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Display omitted