With a taxonomic history extending as far back as 1804, the family was formally recognized by the Swiss palaeontologist Hans Georg Stehlin in 1910 and contains two genera: Amphimeryx and Pseudamphimeryx.

[4] In a palaeontology textbook dating back to 1891–1893, the German palaeontologist Karl Alfred von Zittel classified Amphimeryx to the artiodactyl family Xiphodontidae.

[8] In 1941, the American palaeontologist Edwin H. Colbert wrote about evolutionary affinities of fossil and extant ruminants, comparing Archaeomeryx to other artiodactyl genera like Amphimeryx, Hypertragulus, Gelocus, and Tragulus.

Similarly, American palaeontologists S. David Webb and Beryl E. Taylor in 1980 argued that the Amphimerycidae had historically been tied to the Ruminantia due to postcranial convergences but otherwise had more in common with xiphodonts than ruminants in terms of dentition.

[8][13] While amphimerycids have typically been excluded from the Ruminantia due to dental characteristics, it does not eliminate the possibility of them being sister taxa to ruminants by the latter independently gaining longer legs and more selenodont (crescent-shaped) dentition.

[14] Its affinities, along with those of other endemic European artiodactyls, are unclear; the Amphimerycidae, Anoplotheriidae, Xiphodontidae, Mixtotheriidae, and Cainotheriidae have been determined to be closer to either tylopods (i.e. camelids and merycoidodonts) or ruminants.

[13][15][16] In an article published in 2019, Romain Weppe et al. conducted a phylogenetic analysis on the Cainotherioidea within the Artiodactyla based on mandibular and dental characteristics, specifically in terms of relationships with artiodactyls of the Palaeogene.

They determined that the Cainotheriidae, Robiacinidae, Anoplotheriidae, and Mixtotheriidae formed a clade that was the sister group to the Ruminantia while Tylopoda, along with the Amphimerycidae and Xiphodontidae split earlier in the tree.

[16] The phylogenetic tree used for the journal and another published work about the cainotherioids is outlined below:[17] Eurodexis russelli Dichobune leporina Amphimeryx murinus Xiphodon castrense Paratoceras coatesi Eotylopus reedi Parvitragulus priscus Lophiomeryx chalaniati Archaeomeryx optatus Mixtotherium cuspidatum Anoplotherium latipes Dacrytherium ovinum Robiacina lavergnesis Robiacina minuta Robiacina quercyi Palembertina deplasi Paroxacron bergeri Paroxacron valdense Oxacron courtoisii Cainotherium laticurvatum Caenomeryx filholi Caenomeryx procommunis Plesiomeryx cadurcensis Plesiomeryx huerzeleri In 2020, Vincent Luccisano et al. created a phylogenetic tree of the basal artiodactyls, a majority endemic to western Europe, from the Palaeogene.

The phylogenetic tree as produced by the authors is shown below:[15] Bunophorus Gunophorus Diacodexis Protodichobune Eurodexis Buxobune Mouillacitherium Meniscodon Hyperdichobune Dichobune robertiana Dichobune leporina Homacodon Gobiohyus Khirtharia Entelodon Palaeocheorus Perchoerus Haplobunodon Cuisitherium Lophiobunodon Mixtotherium Robiacina Dacrytherium Diplobune Xiphodon Paraxiphodon Cainotherium Paroxacron Archaeomeryx Amphimeryx Pseudamphimeryx Aumelasia Hallebune Amphirhagatherium Cebochoerus Gervachoerus Choeropotamus Siamotherium In 2022, Weppe conducted a phylogenetic analysis in his academic thesis regarding Palaeogene artiodactyl lineages, focusing most specifically on the endemic European families.

One large monophyletic set consisted of the Hyperdichobuninae, Amphimerycidae, Xiphodontidae, and Cainotherioidea based on dental synapomorphies, of which the hyperdichobunines are paraphyletic in relation to the other clades.

[19][8] Amphimerycids differ from ruminants, particularly the basal clade Tragulina, in the retentions of their first premolars and their high levels of specialization in their selenodonty and number of cusps in their molars.

Modern mammalian orders including the Perissodactyla, Artiodactyla, and Primates (or the suborder Euprimates) appeared already by the Early Eocene, diversifying rapidly and developing dentitions specialized for folivory.

[31] The Holarctic mammalian faunas of western Europe were therefore mostly isolated from other landmasses including Greenland, Africa, and eastern Eurasia, allowing for endemism to develop.

[18][33][36] The stratigraphic ranges of the early species of Amphimeryx also overlapped with metatherians (Herpetotheriidae), cimolestans (Pantolestidae, Paroxyclaenidae), rodents (Ischyromyidae, Theridomyoidea, Gliridae), eulipotyphlans, bats, apatotherians, carnivoraformes (Miacidae), and hyaenodonts (Hyainailourinae, Proviverrinae).

Other mammal genera that cooccur in the site include the herpetotheriids Amphiperatherium and Peratherium, apatemyid Heterohyus, nyctitheriid Saturninia, rodents (Glamys, Elfomys, Plesiarctomys, Ailuravus, Remys), omomyids Pseudoloris and Necrolemur, adapid Adapis, hyaenodonts Paroxyaena and Cynohyaenodon, carnivoraformes Paramiacis and Quercygale, palaeotheres (Propalaeotherium, Anchilophus, Plagiolophus, Pachynolophus, Palaeotherium), lophiodont Lophiodon, hyrachyid Chasmotherium, cebochoerids Acotherulum and Cebochoerus, choeropotamid Choeropotamus, tapirulid Tapirulus, anoplotheriids (Dacrytherium, Catodontherium, Robiatherium), robiacinid Robiacina, and xiphodonts (Xiphodon, Dichodon, Haplomeryx).

[33][37][39][40] The causes of the faunal turnover have been attributed to a shift from humid and highly tropical environments to drier and more temperate forests with open areas and more abrasive vegetation.

[34][35] The MP18 locality of La Débruge of France indicates that A. murinus coexisted with a wide variety of mammals, namely the herpetotheriid Peratherium, rodents (Blainvillimys, Theridomys, Plesiarctomys, Glamys), hyaenodonts (Hyaenodon and Pterodon), amphicyonid Cynodictis, palaeotheres (Plagiolophus, Anchilophus, Palaeotherium), dichobunid Dichobune, choeropotamid Choeropotamus, cebochoerids Cebochoerus and Acotherulum, anoplotheriids (Anoplotherium, Diplobune, Dacrytherium), tapirulid Tapirulus, xiphodonts Xiphodon and Dichodon, cainothere Oxacron, and the anthracothere Elomeryx.

[8][18] The causes of the extinctions of many other mammals in western Europe have been attributed to negative interactions with immigrant faunas (competition, predations), environmental changes from cooling climates, or some combination of the two.