This paper reports the synthesis of novel monodisperse Al2O3-coated molybdenum disulfide nanospheres (i.e., core-shell structures) using a one-step facile hydrothermal method. XPS analysis confirmed the purity and stable structure of the Al2O3-coated MoS2 nanospheres. A possible growth mechanism of the core-shell structure is also reported, along with their influence on the photodegradation process of rhodamine B (RhB). The Al2O3-coated MoS2 nanospheres demonstrate good photocatalytic activity and chemical stability compared to MoS2 spheres. TG-DTA analysis provided insight into the decomposition process of the precursor solution and the stability of the nanoparticles. The enhanced photocatalytic activity makes the Al2O3-coated MoS2 nanospheres a promising candidate as a photocatalyst that could be used in place of traditional Al2O3/MoS2 photocatalyst for the removal of pollutants from waste water.