Described species within this genus lived in the Eocene epoch, with some unnamed or questionable records from Cenomanian and Maastrichtian.

[4] Remains have also been found in North America, including Maryland and Virginia (from the early Eocene Nanjemoy Formation),[5] Georgia[6] and Mississippi.

Subsequently the advanced grade are characterized by vertebrae presenting a strong lateral compression which translate to being much better adaption to aquatic life.

Species of Palaeophis were specialised aquatic animals, as their fossils occur primarily in marine strata, though at least some estuarine remains have also been found.

Studies on Palaeophis vertebrae show a high degree of vascularisation, suggesting that it had a considerably faster metabolism and growth rate than modern snakes.