"Tylosaurus" was the third new genus of mosasaur to be described from North America behind "Clidastes" and "Platecarpus" and the first in Kansas. The early history of the genus as a taxon was subject to complications spurred by the infamous rivalry between American paleontologists Edward Drinker Cope and Othniel Charles Marsh during the Bone Wars. The type specimen was described by Cope in 1869 based on a fragmentary skull measuring nearly in length and thirteen vertebrae lent to him by Louis Agassiz of the Harvard Museum of Comparative Zoology. The fossil, which remains in the same museum under the catalog number MCZ 4374, was recovered from a deposit of the Niobrara Formation located in the vicinity of Monument Rocks near the Union Pacific Railroad at Fort Hays, Kansas. Cope's first publication of the fossil was very brief and was named "Macrosaurus proriger", the genus being a preexisting European mosasaur taxon. The specific epithet "proriger" means "prow-bearing", which is in reference to the specimen's unique prow-like elongated rostrum and is derived from the Latin word "prōra" (prow) and suffix "-gero" (I bear). In 1870, Cope published a more thorough description of MCZ 4374. Without explanation, he moved the species into another European genus "Liodon" and declared his original "Macrosaurus proriger" a synonym.