[3][4] Milk snakes can be found from the southeastern extreme of Ontario, Canada, from southeastern Maine and all the states of the Eastern Seaboard, south to Florida, Alabama, Mississippi; in the midwest, from central Minnesota to Colorado, Nebraska, and the Dakotas; they are found in the foothills of the Appalachian Mountains; Georgia, Tennessee, Kentucky, Arkansas, Kansas, Oklahoma, Texas and Louisiana.

[5][6] Across the wide range of this species, habitat varies; typically, milk snakes prefer to live in forested regions or areas of open woodland.

Depending on subspecies, milk snakes enter hibernation from late October or November to mid-April.

However, unusually large milk snakes can become rather bulkier than average-sized adults and potentially weigh up to 750 to 1,400 g (1.65 to 3.09 lb), though high weights as such are generally reported from captivity.

[12] Generally more tropical populations, from Mexico and further south, reach larger adult sizes than milk snakes living in the temperate zones.

[9][18] Adults' diet is primarily small mammals, but frequently includes lizards (especially skinks).

Although the diet of adult milk snakes primarily consists of rodents[9] (such as voles, mice, and rats),[18] they also have been known to consume a variety of other animals: birds and their eggs, other reptiles, amphibians, and invertebrates.

[2] Milk snakes are oviparous, laying an average of about 10 eggs per clutch, although that number may vary by region.

In June and July, the female lays three to 24 eggs beneath logs, boards, rocks, and rotting vegetation.

[17] The average hatchling in Virginia measures 20.9 cm (8.2 in) in total length and weighs 4.1 g (0.14 oz).

[7] The milk snake is listed as of least concern by the IUCN (a wildlife conservation union),[20] but in some areas, they may face significant pressure due to pet-trade collection.