They were hardy as evidenced by their high species diversity and their presence in a wide variety of environments, extending from the far south of Patagonia (Cueva del Milodón Natural Monument) to Alaska.

[11] Like other xenarthrans, the adult teeth of ground sloths lacked enamel, with the tooth surface being composed of relatively soft orthodentine.

[19] Sloths that had longer snouts are presumed to have had greater olfactory acuity, but appear to have also had less binocular vision and poorer ability to localize sounds.

[22][23] Their skeletal anatomy suggests that they were incapable of running, and relied on other strategies to defend against predators,[24] though they were likely significantly more active and agile than living tree sloths.

[25] Ground sloths were likely able to adopt a bipedal stance while stationary, allowing the forelimbs to be used to grasp vegetation as well as to use their claws for defence, though whether they were capable of moving in this posture is uncertain.

During the Pliocene and Pleistocene, as part of the Great American Interchange, additional lineages of sloths migrated into Central and North America.

[37] Megalonyx, which means "giant claw", was a widespread North American genus that lived past the close of the last (Wisconsin) glaciation, when so many large mammals died out.

[41][42] The earliest known North American megalonychid, Pliometanastes protistus, lived in the southern U.S. about 9 million years ago and is believed to have been the predecessor of Megalonyx.

The group includes the heavily built Megatherium (given its name 'great beast' by Georges Cuvier[44]) and Eremotherium, which are the largest known ground sloths, thought to have had body masses of 3.5-4 tons.

Their thick bones and even thicker joints (especially those on the hind legs) gave their appendages tremendous power that, combined with their size and fearsome claws, provided a formidable defense against predators.

The earliest megatheriid in North America was Eremotherium eomigrans which arrived 2.2 million years ago, after crossing the recently formed Panamanian land bridge.

The last ground sloths in North America belonging to Nothrotheriops died so recently that their subfossil dung has remained undisturbed in some caves.

One of the skeletons, found in a lava tube (cave) at Aden Crater, adjacent to Kilbourne Hole, New Mexico, still had skin and hair preserved, and is now at the Yale Peabody Museum.

The American Museum of Natural History has exhibited a sample of Mylodon dung from Argentina with a note that reads "deposited by Theodore Roosevelt".

[54][55] Based on collagen sequence data showing that its members are more distant from other mylodontids than Choloepodidae, it was elevated back to full family status in 2019.

Chubutherium is an ancestral and very plesiomorphic member of this subfamily and does not belong to the main group of closely related genera, which include Scelidotherium and Catonyx.

[57] Steadman et al. argue that it is no coincidence that studies have shown that ground sloths disappeared from an area a few years after the arrival of humans.

[7] Trackways preserved in New Mexico (probably dating from 10 to 15.6 thousand years ago) that appear to show a group of humans chasing or harassing three Nothrotheriops or Paramylodon ground sloths may record the scene of a hunt.

The tracks are interpreted as showing seven instances of a sloth turning and rearing up on its hind legs to confront its pursuers, while the humans approach from multiple directions, possibly in an attempt to distract it.

[62] A number of kill sites are known for ground sloths in the Americas, these include Campo Laborde in the Pampas of Argentina, where an individual of Megatherium americanum was butchered at the edge of a swamp, dating to approximately 12,600 years Before Present (BP),[63] with another potential Megatherium kill site being Arroyo Seco 2 in the same region, dating to approximately 14,782–11,142 cal yr BP.

[64] In northern Ohio, a Megalonyx jeffersoni skeleton dubbed the "Firelands Ground Sloth" has cut marks indicative of butchery, dating to 13,738 to 13,435 years BP.

[65] At the Santa Elina rockshelter in Mato Grosso Brazil, a specimen of Glossotherium is associated with hearths and stone tools, dating to 11,833–11,804 years BP.

At Fell's Cave in southern Chilean Patagonia, a specimen of Mylodon with fractured and burned bones associated with human activity has been dated to approximately 12,766–12,354 years BP.

[66] By this time, humans had developed proficient hunting weapons, including the Clovis points, which were narrow, carved stone projectiles used specifically for big game.

Analysis of these coproliths have found that ground sloths often ate the foliage of trees, hard grasses, shrubs, and yucca; these plants were located in areas that would have exposed them,[69] making them susceptible to human predation.

[70] While ground sloths would have been relatively easy to spot and approach, big game hunters' weapons would have been useless from farther than 9.1 metres (30 ft) away.