It is widely agreed that the evolutionary lineage of the grey wolf can be traced back 2 million years to the Early Pleistocene species Canis etruscus, and its successor the Middle Pleistocene Canis mosbachensis. The grey wolf Canis lupus is a highly adaptable species that is able to exist in a range of environments and which possesses a wide distribution across the Holarctic. Studies of modern grey wolves have identified distinct sub-populations that live in close proximity to each other. This variation in sub-populations is closely linked to differences in habitat – precipitation, temperature, vegetation, and prey specialization – which affect cranio-dental plasticity.

The earliest specimens of the modern grey wolf date to around 400,000 years ago, or possibly earlier to 1 million years ago. Most modern wolves share most of their common ancestry within the last 25-23,000 years from earlier Siberian wolf populations. While some sources have suggested that this is the result of a population bottleneck, others suggest that this is a normal consequence of gene flow homogenising wolf genomes across their range.

The fossil record for ancient vertebrates is composed of rarely occurring fragments from which it is often impossible to obtain genetic material. Researchers are limited to morphologic analysis but it is difficult to estimate the intra-species and inter-species variations and relationships that existed between specimens across time and place. Some observations are debated by researchers who do not always agree, and hypotheses that are supported by some authors are challenged by others.

The Cretaceous–Paleogene extinction event occurred 66 million years ago and brought an end to the non-avian dinosaurs and the appearance of the first carnivorans. The name carnivoran is given to a member of the order Carnivora. Carnivorans possess a common arrangement of teeth called carnassials, in which the first lower molar and the last upper premolar possess blade-like enamel crowns that act similar to a pair of shears for cutting meat. This dental arrangement has been modified by adaptation over the past 60 million years for diets composed of meat, for crushing vegetation, or for the loss of the carnassial function altogether as in seals, sea lions, and walruses. Today, not all carnivorans are carnivores, such as the insect-eating aardwolf.

The carnivoran ancestors of the dog-like caniforms and the cat-like feliforms began their separate evolutionary paths just after the end of the dinosaurs. The first members of the dog family Canidae appeared 40 million years ago, of which only its subfamily the Caninae survives today in the form of the wolf-like and fox-like canines. The caniforms included the fox-like genus Leptocyon whose various species existed from 34 million YBP before branching 11.9 million YBP into Vulpes (foxes) and Canini (canines). The jackal-sized Eucyon existed in North America from 10 million YBP and by the Early Pliocene about 6–5 million YBP the coyote-like Eucyon davisi invaded Eurasia. In North America it gave rise to early Canis which first appeared in the Miocene (6 million YBP) in south-western US and Mexico. By 5 million YBP the larger Canis lepophagus appeared in the same region.

The canids that had immigrated from North America to Eurasia – Eucyon, Vulpes, and Nyctereutes – were small to medium-sized predators during the Late Miocene and Early Pliocene but they were not the top predators. The position of the canids would change with the arrival of Canis to become a dominant predator across the Holarctic. The wolf-sized C. chihliensis appeared in northern China in the Mid-Pliocene around 4–3 million YBP. The large wolf-sized Canis appeared in the Middle Pliocene about 3 million years ago in the Yushe Basin, Shanxi Province, China. By 2.5 million years ago its range included the Nihewan Basin in Yangyuan County, Hebei, China and Kuruksay, Tadzhikistan. This was followed by an explosion of Canis evolution across Eurasia in the Early Pleistocene around 1.8 million YBP in what is commonly referred to as the wolf event. It is associated with the formation of the mammoth steppe and continental glaciation. Canis spread to Europe in the forms of C. arnensis, C. etruscus, and C. falconeri. Other studies state that the oldest Canis remains that have been found in Europe were from France and dated to 3.1 million YBP, followed by Canis cf. etruscus (where cf. in Latin means confer, uncertain) from Italy dated to 2.2 million YBP.

The fossil record is incomplete but it is likely that wolves arose from a population of small, early canids. Morphological evidence and genetic evidence both suggest that wolves evolved during the Pliocene and Early Pleistocene eras from the same lineage that also led to the coyote, with fossil specimens indicating that the coyote and the wolf diverged from a common ancestor 1.5 million years ago. The ancestor of the jackal and the other extant members of the genus Canis had split from the lineage before this time.

After this separation from a common ancestor the species that were believed to be involved in the further evolution of the wolf and coyote – and the beliefs of some paleontologists – diverged. A number of researchers believed that the lines of C. priscolatrans, C. etruscus, C. rufus, C. lycaon, and C. lupus were components involved in some way that lead to the modern wolf and coyote.