Wire and Arc Additive Manufacturing (WAAM) is a highly efficient production process that enables the low-cost manufacture of complex components used in a wide range of industrial applications. Several studies have been devoted to explore the impact of the WAAM process on the resulting microstructural features and mechanical properties. The purpose of this study is to assess the anisotropic behaviour under tensile stress considering two different extraction directions according to the deposition layer: horizontal (H) and vertical (V) and to correlate results to microstructural features. To achieve this, two 5356 aluminum alloy parts were manufactured by WAAM using different process parameters. Mechanical characterization of WAAM parts were carried out by means of tensile and micro hardness tests. Metallographic analysis was performed to relate micorstructural characteristics induced by the process to the mechanical properties. An anisotropic behavior was revealed considering the sample orientation, with the lowest strength and ductility found for (V) specimens. This anisotropy was correlated with grain size and the presence of larger porosities and discontinuities. This phenomenon was found to be reduced when microstructure presents finer grain size with few microstructural defects. The percentage of anisotropy in tensile strength is reduced from 37.4% to 3.4% and in elongation from 75.8% to 8.3%. In comparison with previous studies, mechanical characterization highlighted very interesting mechanical properties, when adequate process parameters combination was used. These improvements may lead to new potential exploitation in the production of complex designs and optimized geometries for lightweight structural applications.