Mechanical properties and strengthening, deformation, and/or fracture mechanisms of refractory high-entropy alloys VxNbMoTa are investigated. At room temperature, both the yield strength and ductility of VxNbMoTa are greatly improved when increasing the V concentration, which can be related to the enhanced solid solution strengthening and the grain refinement. The fracture morphologies of VxNbMoTa experience the intergranular-to-transgranular transition as increasing the V content. The better ductility of high vanadium alloys should attribute to the refined grains and reduced impurities and brittle compounds at the grain boundary as revealed by atom probe tomography. At 800 °C and 1000 °C, the VxNbMoTa alloys of higher V concentrations exhibit weaker strain hardening rates, while this is opposite at room temperature. This can be explained by the decreased activation energy of hot deformation as increasing the V concentration at elevated temperatures, as indicated by flow stress analyses using the strain-compensated Arrhenius-type model with improved predictability.