SO42-/ZrO2 anchored Nb2O5 nanotubes (SO42-/ZrO2@Nb2O5-NT) are prepared via the high temperature calcination, proton exchange, exfoliation, recombination, and impregnation processes. The structures and anchoring model can be confirmed by XRD, HRTEM, and FT-IR technologies. The acidic properties and specific surface area are characterized by NH3-TPD and N2 adsorption–desorption isotherms. The catalytic performances are evaluated via an esterification reaction of acetic acid and n-butanol. The results show that SO42-/ZrO2@Nb2O5-NT have stronger acid strength and higher acid content than that of Nb2O5-NT. The optimal esterification scheme is as follows: catalyst dosage is 11 wt.%, molar ratio of alcohol to acid is 2.7:1, reaction temperature is 118 ℃, and reaction time is 7 h. The esterification rate can be reached up to 92.31% over SO42-/ZrO2@Nb2O5-NT. We have rationalized esterification performance of these selected catalysts in light of structure–property relationships, which gives useful insight for the development and application of next generation esterification catalyst.