Lophiosilurus alexandri is an endemic catfish from the São Francisco River Basin (Brazil) popularly known as pacamã, which has economic potential for aquaculture farming. The mitochondrial genome was sequenced for the threatened Neotropical catfish L. alexandri. Assembly into scaffolds using MIRA and MITObim software produced the whole, circularized mitochondrial genome, which comprises 16,445 bp and presents the typical gene arrangement of Teleostei mitochondria. A phylogenomic analysis was performed after the concatenation of all proteins obtained from whole mitogenomes of 20 Siluriformes and two outgroups. The results confirmed the monophyly of nine families of catfishes and also clustered L. alexandri as a sister group to the family Pimelodidae, thus confirming the monophyly of the superfamily Pimelodoidea. This is the first mitochondrial phylogenomics study for Pimelodoidea and the first mitogenome described for the Pseudopimelodidae family, representing an important resource for phylogeography, evolutionary biology, and conservation genetics studies in Neotropical fishes.