[4][3] Despite claims of historical translocations from Europe, modern red fox populations in the United States' southeastern region have been shown to be native to North America.

[5] DNA comparisons show that the eastern American red fox is closely related to native populations in Canada and the northeastern region of the United States and is, therefore, the result of natural range expansions and not an invasive species from Europe as was previously thought.

[4] Gene mapping demonstrates that red foxes in North America have been isolated from their Old World counterparts for over 400,000 years, thus raising the possibility that speciation has occurred.

Fossils dating from the Wisconsian are present in 25 sites in Arkansas, California, Colorado, Idaho, Missouri, New Mexico, Ohio,[9] Tennessee, Texas, Virginia and Wyoming.

The northern (or boreal) refugium occurs in Alaska and western Canada and consists of the large subspecies V. v. alascensis, V. v. abietorum, V. v. regalis and V. v. rubricosa.

The southern (or montane) refugium occurs in the sub-alpine parklands and alpine meadows of the Rocky Mountains, the Cascade Range and the Sierra Nevada and consists of the small subspecies V. v. cascadensis, V. v. macroura, V. v. necator and V. v. patwin.

[3][15] The eastern American red fox generally prefers mixed vegetation communities that occur on edge habitats with a high level of diversity.

[15] Food sources can vary depending on region, but cottontail rabbits (Sylvilagus) are the most important prey for eastern American red foxes.