The advent of additive manufacturing (AM), also known as 3D printing, has revolutionized the production of titanium alloys, offering significant advantages in fabricating complex geometries with enhanced mechanical properties. This study investigates the variant-specific deformation mechanisms in HIP-treated TA15 (Ti-6.5Al-2Zr-1Mo-1V) titanium alloy, fabricated via selective electron beam melting (SEBM). The alloy exhibits a dual-phase (α+β) microstructure, where six distinct α variants are formed through the β→α phase transformation following the Burgers orientation relationship. Variant selection during AM leads to a non-uniform distribution of these α variants, with α6 (22.3%) dominating due to preferential growth. Analysis of the prismatic slip Schmid factor reveals that α4–α6 variants, with higher Schmid factors (>0.45), primarily undergo prismatic slip, while α1–α3 variants, with lower Schmid factors (<0.3), rely on basal or pyramidal slip and twinning for plastic deformation. In-grain misorientation axis (IGMA) analysis further reveals strain-dependent slip transitions: pyramidal slip is activated in α1–α3 variants at lower strains, while prismatic slip becomes the dominant deformation mechanism in α4–α6 variants at higher strains. Additionally, deformation twins, primarily {10–12} extension twins (7.1%), contribute to the plasticity of hard-oriented α variants. These findings significantly enhance the understanding of the orientation-dependent deformation mechanisms in HIPed TA15 alloy and provide a crucial basis for optimizing the performance of additively-manufactured titanium alloys.