In this study, 2219 aluminum alloy thick plate was joined by electron beam welding. Defect-free joints with excellent surface formation were obtained. There were significant differences in the microstructure along the thickness direction of the weld zone (WZ). The upper region of the WZ was mainly striated grains, while the lower region was fine equiaxed grains. The WZ of 2219 joint is composed of α-Al and Al-Cu eutectic. Fine equiaxed grains were formed in the partially melted zone (PMZ) due to the existence of high-melting nucleation particles including Ti-Al and Ti-Zr compounds. The eutectic microstructure in the PMZ and the heat-affected zone (HAZ) presented net-like and block-shape distribution. Due to the formation of fine grains and high content of Al-Cu eutectic, the WZ showed the highest microhardness (80 HV). Therefore, the 2219 joint obtained excellent mechanical properties. The tensile strength of the 2219 joint was equal to that of the base metal (BM), but the elongation of the 2219 joint significantly decreased to 15.1%, about 67.7% of that of BM. The fracture mode of the 2219 joint presented typical ductile fracture.