True eels diverged from other ray-finned fish during the Jurassic, while cusk-eels are part of the Percomorpha clade, along with tuna, perch, seahorses and others.

The oldest fossil cusk-eel is Ampheristus, a highly successful genus with numerous species that existed from the Late Cretaceous (Maastrichtian) to the early Oligocene.

Due to the inconsistencies in specific morphological characteristics in closely related species, attempts to use different characters, such as the position of pelvic fins, to classify Ophiididae into distinct families has proven highly unsatisfactory.

Unlike true eels of the order Anguilliformes, cusk-eels have ventral fins that are developed into a forked barbel-like organ below the mouth.

These larvae live amongst the plankton relatively close to the water's surface[3] and are believed to control their metamorphoses into adult cusk-eels, dispersing over greater distances into less utilized habitats and reducing competition in concentrated areas.