Ti–48Al–2Cr–2Nb (Ti4822) alloy was manufactured by the electron beam melting (EBM) process, and its microstructure and compressive deformation behavior at room and high temperatures (25, 600, 750, 900, and 1050 °C) were investigated. In addition, plasma-melted Ti4822 alloy was manufactured as a reference material to compare the microstructure and mechanical properties. EBM-built Ti4822 has a near-gamma structure composed of equiaxed γ phase (L10 structure) with α2 (D019 structure) phase at the interface of γ phase, whereas plasma-melted Ti4822 has a fully lamellar structure. Temperature-dependent compression tests identified that EBM-built Ti4822 has relatively low yield strength in all temperature ranges compared to plasma-melted reference material. However, in the case of ductility, EBM-built Ti4822 has higher fracture strain compared with plasma-melted Ti4822. The reason for this behavior is the microstructural differences found between EBM-built and plasma-melted Ti4822. In the high-temperature compressive results, yield stress anomaly (YSA) phenomena occurred in a certain temperature range with both alloys. The room temperature deformed microstructure shows that EBM-built Ti4822 accommodated deformation by dislocation glide and twinning, while plasma-melted Ti4822 could not fully accommodate the deformation. In addition, dynamic recrystallization (DRX) occurred at above 900 °C in the EBM-built Ti4822, and above 750 °C in the plasma-melted Ti4822, suggesting that different DRX behavior appeared in high temperature deformation. Based on the above findings, this study further analyzed the correlation between the microstructure and the room- and high-temperature deformation mechanism of EBM-built Ti–48Al–2Cr–2Nb.