This is a list of mammals that are or were in the past native to South Carolina.
- Balaenopteridae
- Bowhead whale (Balaena mysticetus)
- Fin whale (Balaenoptera physalus)
- Humpback whale (Megaptera novaengliae)
- Minke whale (Balaenoptera acutorostrata)
- Right whale (Eubalaena glacialis)
- Sei whale (Balaenoptera borealis)
- Bovidae
- Bison (Bison bison)
- Canidae
- Coyote (Canis latrans)
- Fox
- Grey fox (Urocyon cinereoargenteus)
- Red fox (Vulpes vulpes)
- Wolf
- Gray wolf (Canis lupus)
- Red wolf (Canis rufus)
- Cervidae
- Elk (Cervus elaphus)
- White-tailed deer (Odocoileus virginianus)
- Dasypodidae
- Nine-banded armadillo (Dasypus novemcinctus)
- Delphinidae
- Antillean beaked whale (Mesoplodon europaeus)
- Atlantic pilot whale (Globicephala melaena)
- Atlantic spotted dolphin (Stenella frontails)
- Common bottlenose dolphin (Tursiops truncatus)
- Dense-beaked whale (Mesoplodon densirostris)
- False killer whale (Pseudorca crassidens)
- Grampus (Grampus griseus)
- Pantropical spotted dolphin (Stenella attenuata)
- Rough-toothed dolphin (Steno bredanenis)
- Saddleback dolphin (Delphinus delphis)
- Short-finned pilot whale (Globicephala macrohyncha)
- Spinner dolphin (Stenella longirostris)
- Striped dolphin (Stenella coeruleoalba)
- True's beaked whale (Mesoplodon mirus)
- Didelphimorphia
- Virginia opossum (Didelphis virginiana)
- Equidae
- Horse (Equus caballus)
- Eschrichtiidae
- Gray whale (Eschrichtius robustus)
- Felidae
- Bobcat (Lynx rufus)
- Mountain lion (Puma concolor)
- Leporidae
- Eastern cottontail (Sylvilagus floridanus)
- Marsh rabbit (Sylvilagus palustris)
- New England cottontail (Sylvilagus transitionalis)
- Swamp rabbit (Sylvilagus aquaticus)
- Molossidae
- Brazilian free-tailed bat (Tadarida brasiliensis)
- Muridae
- Black rat (Rattus rattus)
- Cotton mouse (Peromyscus gossypinus)
- Deer mouse (Peromyscuc maniculatus)
- Eastern harvest mouse (Reithrodontomys humulis)
- Eastern woodrat (Neotoma Floridana)
- Golden mouse (Ochrotomys nuttalli)
- Hispid cotton rat (Sigmodon hispidus)
- House mouse (Mus musculus)
- Meadow vole (Microtus pennsylvanicus)
- Muskrat (Ondatra zibethiscus)
- Norway rat (Rattus norvegicus)
- Oldfield mouse (Peromyscus polionotus)
- Pine vole (Microtus pinetorum)
- Red-backed vole (Clethrionomys gapperi)
- Rice rat (Oryzomys palustris)
- White-footed mouse (Peromyscus leucopus)
- Mustelidae
- Least weasel (Mustela nivalis)
- Long-tailed weasel (Mustela frenata)
- Mink (Mustela vison)
- North American river otter (Lutra canadensis)
- Spotted skunk (Spilogal putorius)
- Striped skunk (Mephitis mephitis)
- Phocidae
- Harbor seal (Phoca vitulina)
- Hooded seal (Cystophora cristata)
- Phocoenidae
- Harbor porpoise (Phocoena phocoena)
- Physeteridae
- Dwarf sperm whale (Kogia simus)
- Pygmy sperm whale (Kogia breviceps)
- Sperm whale (Physeter catodon)
- Procyonidae
- Raccoon (Procyon lotor)
- Sciuridae
- Eastern chipmunk (Tamias striatus)
- Grey squirrel (Sciurus carolinensis)
- Least shrew (Cryptotis parva)
- Masked shrew (Sorex cinereus)
- Southern short-tailed shrew (Blarina carolinensis)
- Soricidae
- American pygmy shrew (Microsorex hoyi)
- Red squirrel (Tamiasciurus hudsonicus)
- Short-tailed shrew (Blarina brevicauda)
- Smoky shrew (Sorex fumeus)
- Southeastern shrew (Sorex longirostris)
- Southern flying squirrel (Glaucomys volans)
- Woodchuck (Marmota monax)
- Suidae
- Wild boar (Sus scrofa)
- Talpidae
- Eastern mole (Scalopus aquaticus)
- Hairy-tailed mole (Parascalops breweri)
- Star-nosed mole (Condylura cristata)
- Trichechidae
- Manatee (Trichechus manatus)
- Ursidae
- Black bear (Ursus americanus)
- Vespertilionidae
- Big brown bat (Eptesicus fuscus)
- Eastern pipistrelle (Pipistrellus subflavus)
- Eastern red bat (Lasiurus borealis)
- Eastern small-footed bat (Myotis leibii)
- Evening bat (Nycticeius humeralis)
- Hoary bat (Lasiurus cinereus)
- Indiana bat (Myotis sodalis)
- Little brown bat (Myotis lucifugus)
- Northern long-eared bat (Myotis septentrionalis)
- Northern yellow bat (Lasiurus intermedius)
- Rafinesque's big-eared bat (Plecotus rafinesqueii)
- Seminole bat (Lasiurus seminolus)
- Silver-haired bat (Lasionycteris noctivagans)
- Southeastern myotis (Myotis austroriparius)
- Zapodidae
- Meadow jumping mouse (Zapus hudsonius)
- Woodland jumping mouse (Napaeozapus insignis)
- Ziphiidae
- Goosebeaked whale (Ziphius carvirostris)
