There is a lack of efficient methods for removing microcystins produced by cyanobacterial blooms. Here, microsphere-like bismuth vanadate (BiVO4-60) mesocrystals using a simple solvothermal method were prepared and applied to the photocatalytic degradation of microcystin-LR. The results show that the self-assembly of BiVO4 mesocrystals is mainly due to the coordination between acetone and BiO+. The surface area normalized rate constant (kSA) of microcystin-LR degradation for BiVO4-60, of 4.02 × 10–3 L/m2/min, is 3.56 times higher than that of BiVO4-0, of 1.13 × 10–3 L/m2/min. This enhanced photocatalytic activity is explained by the direct oxidation of photogenerated h+ produced on the (110)-oxidation facets. Moreover, BiVO4-60 mesocrystals exhibit stable dispersion and photostability during microcystin-LR degradation. Overall, our findings demonstrate a facile strategy for synthesizing BiVO4 mesocrystals, and provides a promising technology for degrading microcystin-LR.