The effects of deformation temperature and deformation degree on the microstructure and mechanical properties of TC18 titanium alloy during the β isothermal forging were studied. Results show that the microstructure of TC18 titanium alloy is sensitive to the variation of isothermal forging temperature. Deforming in (α+β)-phase gets a typical bi-modal microstructure while deforming in β-phase gets a net-shaped microstructure. When deforming above the β-transus temperature, the forging shows higher strength, fracture toughness and lower plasticity. With higher deformation temperature, both the strength and the plasticity decrease while the fracture toughness increases a little. Deforming above the β-transus temperature, typical Widmanstatten, coarse β grains, and the highest fracture toughness are obtained in small deformation degree. When the deformation degree reaches 60%, grains crack seriously, secondary lamellar α further globalize and disperse, and the microstructure becomes even fine, so the alloy’s strength and plasticity maintain good matching, fracture toughness is better and the best comprehensive properties are achieved