The holotype, consisting of an angular and a basicranium fragment discovered near Hornerstown, New Jersey, already revealed a relatively unique combination of features and prompted a new genus to be described.

The genus remains a key taxon in mosasaur systematics due to its unique set of features and as the most complete representative of its subfamily, the Halisaurinae.

Russell in his Systematics and Morphology of American Mosasaurs (1967) that the angular resembles that of Platecarpus but is more symmetrically heart-shaped in anterior aspect and appears slightly inflated in later profile with a convex anteroventral outline that is continuous with the anteroexternal margin of the articular surface, as in the genus Clidastes.

[4] Several discoveries throughout the 1980s and 1990s helped shed light on Halisaurus, with more complete specimens of the type species H. platyspondylus being discovered and Phosphorosaurus ortliebi being momentarily reassigned to the genus by Lingham-Soliar (1996).

With the description of Eonatator as a closely related genus to Halisaurus, the two genera were grouped into the new subfamily Halisaurinae, which was then believed to be a sister-group to more advanced mosasaurs.

[2] The most recent major phylogenetic analysis of mosasaurs, conducted by Tiago R. Simões and colleagues in May 2017, recovered Halisaurus and the rest of the Halisaurinae as a sister group to the Mosasaurinae.

Below is a cladogram following an analysis by Takuya Konishi and colleagues (2015) done during the description of Phosphorosaurus ponpetelegans, which showcases the internal relationships within the Halisaurinae, showing Halisaurus as the basalmost genus of the subfamily.

Though the designation of these remains as Halisaurus is debatable in most cases, unnamed species are known from the Campanian of Texas, the Maastrichtian of California and the Santonian of Peru (which significantly expands the known temporal range of the genus).

[7] In 2023, Shaker et al. named H. hebae, a new species of Halisaurus from the Late Cretaceous Dakhla Formation of Egypt, on the basis of disarticulated cranial elements, teeth, and vertebrae from the neck and back.

The type specimen, MNHN PMC 14, is an incomplete skeleton that includes a disarticulated skull and 27 associated articulated vertebrae from the Grand Daoui area near Khouribga in central Morocco.