The high cost of development and raw materials have been obstacles to the widespread use of titanium alloys. In the present study, the high-throughput experimental method of diffusion couple combined with CALPHAD calculation was used to design and prepare the low-cost and high-strength Ti-Al-Cr system titanium alloy. The results showed that ultra-fine α phase was obtained in Ti-6Al-10.9Cr alloy designed through the pseudo-spinodal mechanism, and it has a high yield strength of 1437 ± 7 MPa. Furthermore, application of the 3D strength model of Ti-6Al-xCr alloy showed that the strength of the alloy depended on the volume fraction and thickness of the α phase. The large number of α/β interfaces produced by ultra-fine α phase greatly improved the strength of the alloy but limited its ductility. Thus, we have demonstrated that the pseudo-spinodal mechanism combined with high-throughput diffusion couple technology and CALPHAD was an efficient method to design low-cost and high-strength titanium alloys.