It is native to South America, where it occurs in the middle Rio Negro in Brazil.

One record of the species' occurrence refers to a "río Cicipa", which is thought to possibly correspond with the Siapa River, a tributary of the Casiquiare in Venezuela.

Its specific epithet, weberi, honors Claude Weber of the Natural History Museum of Geneva, for his contributions to knowledge of the genus Hypostomus.

[2] The fish is named in honor of Claude Weber, of the Muséum d’Histoire Naturelle de Génève, because of his contributions to the knowledge of the genus.

[3] H. weberi sometimes appears in the aquarium trade, where it is frequently referred to either as Weber's pleco or by its associated L-number, which is L-167.