In this study, microstructures and properties of 2099 Al-Li alloy were investigated during the thermo-mechanical processing. Treated by two-step homogenization treatment (12 h at 510°C+36 h at 530°C), the coarse dendritic structures cannot be observed in the alloy. At the same time, the level of grain boundary segregation was lowered, and a few of small AlCuFeMn/AlCuMn particles remained at the grain boundaries. Following homogenization treatment, the alloy was extruded at 470°C. During extrusion process, dynamic recrystallization occurred in the surface layer of alloy, and the depth of dynamic recrystallized layer increased with solution treating at 540°C. The central zone of alloy with solution treatment exhibited {111}<112> and {111}<110> textures, while {112}<110> texture presented at the surface zone. The corresponding central hardness of alloy in central zone was 95 HV, and the surface hardness was 120 HV. After solution treatment, two-step aging treatment was followed. In the peak-aged condition (12 h at 121°C+48 h at 152°C), a large amount of T1 phases as well as δ′ phases precipitated in the matrix. The tensile strength, yield strength and elongation of alloy on peak aging were 613MPa, 575MPa, and 7.9%, respectively. The SCC susceptibility of alloy decreased with aging time, and the strength loss rate of alloy on over-aging was 5.5%.