Box jellyfish (Class Cubozoa) are known for being particularly dangerous to humans due to exceptionally potent venoms, which is attributed to the presence and abundance of a cnidarian specific pore-forming toxin family called jellyfish toxins (JFTs). These highly hemolytic and cardiotoxic components have previously been reported in species outside of Cubozoa, but no formal analysis of JFT distribution across the cnidarian subphylum Medusozoa has been conducted. We present a thorough annotation of JFTs from 143 publicly available cnidarian transcriptomes and document 109 putative JFTs within over 20 medusozoan species. Phylogenetic analyses show that JFTs form two distinct clades, called JFT-1 and JFT-2. JFT-1 includes all previously characterized cubozoan JFTs as well as representatives from Hydrozoa (hydra, hydromedusae) and Scyphozoa (true jellyfish). JFT-2 is primarily composed of hydrozoan toxins of unknown function. Using selection analyses, we found that a subset of cubozoan JFT-1 sequences are influenced by gene-wide positive episodic selection when compared to JFT-1 toxins from other taxonomic groups, suggesting duplication followed by subfunctionalization as a potential mechanism for the increased venom potency within cubozoans, possibly driven by a dietary shift to vertebrates. Additionally, using published RNA-seq data we found that JFTs are expressed in developing or mature medusae in several species as well as the prey-capture polyps of a colonial hydrozoan. Overall, our findings show a complex evolutionary history of JFTs involving duplication and functional diversification that likely resulted in highly toxic cubozoan venoms, and consequently dangerous envenomation of humans.