Hybrid additive manufacturing, incorporating additive manufacturing (AM) and other thermo-mechanical processes, has been developed to improve AM mechanical properties by modifying the as-deposited microstructure and eliminating defects. Additive manufactured parts present strong anisotropic properties, as shown by the anisotropic columnar grain morphology and texture. Samples of AM Inconel 718 were tested at high temperature and under uniaxial compression over a range of conditions. The evolution of microstructural anisotropy and the viscoplastic behaviour under these hot deformation processes was studied. The microstructure and texture evolution were characterised with optical microscopy (OM), scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The results show that the initial anisotropic microstructure had a negligible effect on flow stress and slip system activation during the hot deformation. The shape of original grains did, however, play a predominant role in determining the final microstructure. When the compression direction was perpendicular to the longitudinal of columnar grains, a more uniform microstructure was obtained under high-flow-stress conditions. This preferred compression direction provides guidance for hot deformation in hybrid additive manufacturing practice. Furthermore, for the nickel alloy studied, controlling the deformation direction to achieve a fine grain structure at a lower temperature (950 °C, lower than δ-solvus) brings practical benefits in the form of possible further δ grain refinement and less demanding thermal conditions during subsequent deformation processes.