Electric fishes have played important roles historically in science, helping to elucidate the very nature of electricity, and in determining the first structures and functions of ion transporters. Despite their historical importance, no study has comprehensively determined the molecular nature of electric organs (EOs), nor have any studies compared EOs in distinct lineages of electric fishes on a large scale. Hundreds of species of electric fish have been described across diverse taxa, the vast majority of which are capable of producing only weakly electric organ discharges (EODs) for the purposes of navigation and communication. The strong-voltage electric eel (Electrophorus electricus) is unique among the Gymnotiformes (the electric fish order to which it belongs) as it also has the ability to generate high-voltage discharges (in excess of 600 volts) for the purposes of predation and defense. We characterized the genome of E. electricus, and sequenced mRNA from eight tissues, including the three EOs found in this species and skeletal muscle. Next, we used comparative transcriptomics to study the sequence and abundance of transcripts found in EO and muscle in two additional Gymnotiformes species, and in two lineages of fish that have independently evolved EOs. We found similar patterns of gene expression in the EOs of these fishes despite their independent origins, notably of transcription factors and signaling pathways that may represent a common genetic toolkit important for the independent evolution of EOs. Finally, we used a quantitative proteomic and phosphoproteomic approach to characterize each of the three distant EOs in E. electricus, and found differences among the EOs we hypothesize may reflect their distinct functions. Together, this represents the first major effort at characterizing a novel tissue type, the EO, both within a species and across diverse species.