As a mosasaur, "Tylosaurus" is classified within the family Mosasauridae in the superfamily Mosasauroidea. The genus is the type genus of its own subfamily, the Tylosaurinae. Other members of this group include "Taniwhasaurus" and possibly "Kaikaifilu", and the subfamily is defined by a shared feature of an elongated conical rostrum that does not bear teeth. The closest relatives of the Tylosaurinae include the Plioplatecarpinae and the primitive subfamilies Tethysaurinae and Yaguarasaurinae; together they are members of one of three possible major lineages of mosasaurs (the others being the Mosasaurinae subfamily and Halisauromorpha group) that was first recognized in 1993. This clade was named the Russellosaurina by Polcyn and Bell in 2005.