A homogeneous HfNbTaTiZr high-entropy alloy was successfully processed via powder metallurgy route. For the initial powder feedstock material fabrication, the electrode induction-melting gas atomization procedure was used, resulting in a spherical powder morphology and dual bcc phase composition distinguishable within the individual particles. Spark plasma sintering was then used for the powder compaction at sintering temperatures ranging from 800 to 1600 °C. By the characterization of the compact microstructures, lattice defects (microscopic porosity and vacancy-like misfit defects), and mechanical properties (hardness and three-point bending strength), the sintering conditions were optimized to obtain a fully dense, homogeneous, single-phase bcc material. It was found that such properties are achieved when sintering at 80 MPa pressure for 2 min at temperatures above 1200 °C, where the single bcc phase structure exhibited ductile behavior with considerable flexural strength and ductility at ambient temperature. Positron annihilation spectroscopy was used to characterize the evolution of atomic and mesoscale defects during optimization of the sintering process.