The invention provides a preparation method of a TC21 titanium alloy large-specification bar, which comprises the following steps: 1, carrying out cogging forging on a TC21 titanium alloy ingot to obtain a primary forging stock; 2, carrying out upsetting forging on the primary forging stock to obtain an intermediate forging stock; 3, carrying out homogenization treatment; 4, carrying out forming forging on the intermediate forging stock to obtain the cylindrical TC21 titanium alloy large-specification bar with a section diameter of 160 mm to 400 mm. According to the invention, by carrying out homogenization treatment and optimizing a forging process, control of an alloy from an equiaxed structure to a tristate structure can be implemented, so that comprehensive regulation and control on intensity, plasticity, toughness and fatigue property are implemented. The preparation method adopts a simple and feasible process; the prepared TC21 alloy large-specification bar has uniform and fine tissues and high mechanical property, is suitable for large-scale industrial production and meets the development requirements of the aerospace industry on the high-quality large-specification TC21 titanium alloy bar.