The performance of solid catalysts and catalyst supports is generally believed to be dependent on their morphology, surface area, and architecture. In order to fully exploit their attractive properties in actual practical applications, layered zirconium phosphate materials should be fabricated into macroscopic form. Here, we report the fabrication of microscopic spheres of α-zirconium phosphate (α-ZrP) by a spray-drying process. The layered α-ZrP nanoparticles were originally obtained using a synthesis route involving separate nucleation and aging steps (SNAS). The resulting products are composed of nanosize α-ZrP particles aggregated into solid microspheres with a diameter of 5–45μm and a sphericity of 0.80. After calcination at 573K, surface area of 43.8m 2 /g could be obtained for α-ZrP microspheres, which is larger than that of the α-ZrP powder after similar thermal treatment (36.2m 2 /g). Furthermore, the number of acidic sites of the α-ZrP microspheres is greater than for the α-ZrP powder due to its unique textual properties and higher surface area. The acylation reaction of fatty acid methyl esters (methyl stearate) with ethanolamine to form monoethanolamides was chosen as a probe reaction to evaluate the catalytic activity of the resulting microspherical α-ZrP materials, which showed high activity compared to the sample in the form of powders, with about 92.9% methyl stearate conversion at 393K for 12h. The enhanced performance in the reaction is determined by the large surface area and the increased number of acidic sites in the multiple-scales porosity of α-ZrP microspheres.