Despite the ecological importance of deep-sea cephalopods, little is known about their genetic diversity or population dynamics. The cephalopod species Cranchia scabra, Pyroteuthis margaritifera, and Vampyroteuthis infernalis are commonly collected in midwater samples from both the Gulf of Mexico and northwestern Atlantic Ocean but, despite their common appearance in trawls and important roles in marine food webs, no genetic studies of population connectivity exist for these species. Here, Sanger sequencing of three conserved genetic loci and ddRADseq techniques were used to examine population genetic dynamics in these deep-sea species. Genetic diversity is lowest in C. scabra, which appears to be in a population growth stage, and highest in V. infernalis. Population structure was unique to V. infernalis but does not appear to be the result of ocean-basin vicariance, thus possible alternative explanations are explored, specifically environmental variation in dissolved oxygen. The genetic connectivity between these geographically disparate sites suggests these three cephalopod species could be resilient to localized environmental disturbances in the Gulf of Mexico.