Rare-earth zirconates are proven to be very effective in restricting the CMAS attack against thermal barrier coatings (TBCs) by forming quick crystalline reaction products that seal the porosity against infiltration. The microstructural effects on the efficacy of Electron Beam-Physical Vapor Deposition gadolinium zirconate (EB-PVD GZO) against CMAS attack are explored in this study. Four distinct GZO microstructures were manufactured and the response of two selected GZO variants to different CMAS and volcanic ash melts was studied for annealing times between 10 min and 50 h at 1250 °C. A significant variation in the microstructural characteristics was achieved by altering substrate temperature and rotation speed. A refined microstructure with smaller intercolumnar gaps and long feather arms lowered the CMAS infiltration by 56%–72%. Garnet phase, which formed as a continuous layer on top of apatite and fluorite, is identified as a beneficial reaction product that improves the CMAS resistance.