Because O. simus was originally named based on poorly preserved fossil material, the genus Ornithocheirus has suffered enduring problems of zoological nomenclature.

Fossil remains of Ornithocheirus have been recovered mainly from the Cambridge Greensand of England, dating to the beginning of the Albian stage of the early Cretaceous period, about 110 million years ago.

[3][4] During the 19th century, in England many fragmentary pterosaur fossils were found in the Cambridge Greensand, a layer from the early Cretaceous, that had originated as a sandy seabed.

[5] Young researcher Harry Govier Seeley was commissioned to bring order to the pterosaur collection of the Sedgwick Museum in Cambridge.

Between the years 1869 and 1870, Seeley each gave them a separate species name: O. simus, O. woodwardi, O. oxyrhinus, O. carteri, O. platyrhinus, O. sedgwickii, O. crassidens, O. capito, O. eurygnathus, O. reedi, O. cuvieri, O. scaphorhynchus, O. brachyrhinus, O. colorhinus, O. dentatus, O. denticulatus, O. enchorhynchus, O. xyphorhynchus, O. fittoni, O. nasutus, O. polyodon, O. tenuirostris, O. machaerorhynchus, O. platystomus, O. microdon, O. oweni and O. huxleyi, thus 27 in total.

[6][7][8] When Seeley published his conclusions in his 1870 book The Ornithosauria, this provoked a reaction by the leading British paleontologist of his day, Sir Richard Owen.

Owen was not an evolutionist and he therefore considered the name Ornithocheirus to be inappropriate; he also thought it was possible to distinguish two main types within the material, based on differences in snout form and tooth position — the best fossils consisted of jaw fragments.

[10] In 1888, Edwin Tulley Newton reassigned several existing species names into Ornithocheirus, which created new combinations: O. clavirostris, O. daviesii, O. sagittirostris, O. validus, O. giganteus, O. clifti, O. diomedeus, O. nobilis, O. curtus, O. macrorhinus and O. hlavaci.

Hooley's classification however, was rarely applied later in the century, and therefore paleontologists weren't aware of it, and kept subsuming all the poorly preserved and confusing material under the name Ornithocheirus.

This situation caused a renewed interest in the Ornithocheirus material and the validity of the several names based on it, for it might be possible that it could by more detailed studies be established that the Brazilian pterosaurs were actually junior synonyms of the European types.

[17] As a result, though over forty species have been named in the genus Ornithocheirus over the years, only O. simus is currently considered valid by all pterosaur researchers.

[25] O. buenzeli (Bunzel 1871, often misspelled and incorrectly attributed as O. bunzeli, Seeley 1881), cited in the past as evidence of Late Cretaceous ornithocheirids,[26] has since been re-identified as a likely azhdarchid as well.

[29] In 2019, Pêgas et al. found Ornithocheirus to be in a basal member of the clade Ornithocheirae, reclassifying all other snout-crested pterosaurs in the family Anhangueridae.