The α + β titanium alloy TC19 (Ti-6Al-2Sn-4Zr-6Mo, mass fraction, %) has shown great application potential in aerospace because of its superior moderate-temperature mechanical properties. The bulk composition of this alloy contains Al, Sn, Zr, and Mo, which are the main alloying elements in the field of high-temperature titanium alloys. Compared with Ti, Al and Sn, which are characterized by lower melting points and densities, can be easily volatilized during vacuum arc remelting (VAR). In addition, Zr has a higher density, and Mo has a higher melting point and density compared with Ti. Therefore, controlling the chemical homogeneity either in the macro- or micro-scale for industrial-scale titanium alloy ingot with complex compositions is challenging. In this study, the macrosegregation behavior and mechanism of Zr and Mo were investigated systematically in a TC19 industrial-scale ingot (ϕ720 mm × 1160 mm) by using a directional solidification technology where samples were solidified under a constant-temperature gradient of approximately 200^oC/cm and a wide range of withdrawal rates (solidification rate) from 3 mm/h to 150 mm/h. Result shows an evident macrosegregation of Zr and Mo, which is primarily attributed to the difference in the solidification rate during solidification. Zr as the negative segregation element was pushed to the front of the solid-liquid interface continuously, whereas Mo as the positive segregation element was enriched in the solid phase at the solid-liquid interface. Consequently, the content of Zr is relatively lower at the center equiaxed crystal zone but higher at the top casting riser in the TC19 industrial-scale ingot. However, Mo exhibits the opposite trend in comparison with Zr. The degree of element segregation decreased with the increase of the solidification rate. Moreover, the “crystal rain” caused by the density difference between liquid and solid phases as well as buoyancy would promote the macrosegregation in industrial-scale ingots. The Lorentz force arising from electromagnetic stirring is the main driving force for the flow of the molten pool during VAR. Electromagnetic stirring plays an important role in accelerating the melt flow in the molten pool, and the strong melt flow is favorable to break the correspondence between the grain structure, thereby weakening macrosegregation. Therefore, the low-temperature gradient and low solidification rate, that is, near equilibrium solidification conditions, primarily cause the macrosegregation in TC19 titanium alloy industrial-scale ingots.