The hot workability of metallic materials is significantly dependent on its ability to form plastic without cracking and fracturing. In this work, the cracking behavior of powder metallurgy (PM) Ti-5Al-5Mo-5V-3Cr (Ti-5553) alloy, consolidated from powder mixture, at a deformation temperature range of 600 °C–850 °C and strain rate of 0.1 s−1–10 s−1, was investigated through isothermal compression tests. The cracking behavior of the as-cast ingot metallurgy (IM) Ti-5553 alloy, at a deformation temperature of 700 °C was also investigated for comparison. Results suggested that the PM Ti-5553 alloy had a better hot workability, with a larger cracking-free processing window, and a lower deformation resistance than the IM counterpart. 45° shear fracture occurred in the PM alloy, compressed at the condition of 600 °C/10 s−1, and edge cracking was observed at the 700 °C/10 s−1. 45° shear fracture was also significant in the IM alloy specimen tested at 700 °C/10 s−1, and all the other IM alloy specimens compressed at 700 °C displayed longitudinal cracking. Moreover, the microscopic cracking observation showed that ductile dimple cracking can be found in the IM alloy, but brittle cleavage fracture was dominant in the cracking surface of PM alloy with a relatively low cracking ductility.