It crops out to the east of the Rocky Mountain Overthrust Belt, and the western portion (about 600 metres or 2,000 feet thick) of this formation is folded and faulted while the eastern part, which thins out into the Sweetgrass Arch, is mostly undeformed plains.

Below the formation are the nearshore (beach and tidal zone) deposits of the Virgelle Sandstone, and above it is the marine Bearpaw Shale.

Throughout the Campanian, the Two Medicine Formation was deposited between the western shoreline of the Late Cretaceous Interior Seaway and the eastward advancing margin of the Cordilleran Overthrust Belt.

[1] During this time frame only three species were named and of these only Styracosaurus ovatus and Edmontonia rugosidens are still regarded as valid.

The loosely consolidated fine grain sediments composing the formation allow for fast plant growth in badland areas, limiting the number of exposed outcrops.

The Two Medicine overlies the Virgelle Sandstone, which formed from the beach sands exposed on northern and western shores of the receding Colorado Sea.

[6] A Cretaceous Interior Seaway transgression submerged the area briefly early on in Two Medicine history leaving anomalous paralic sediments and isolated shale bodies about 100 m above the base of the formation.

The extensive red beds and caliche horizons of the upper Two Medicine are evidence of at least seasonally arid conditions.

[8] The sediments of the Horsethief represent shallower water deposits than the Bearpaw Shale adding further evidence of higher elevation areas existing in the south.

It is a colonial nesting site on the Willow Creek Anticline in the Two Medicine Formation that is famous for its fossil eggs of Maiasaura, which demonstrated for the first time that at least some dinosaurs cared for their young.

The parent(s) must then have brought food to the young, and there is plant matter in the nests that may be evidence of either this or for incubation of the eggs.

[9] Later research came to find that the supposedly distinct dinosaur faunas at different levels of the formations were more similar than had been previously thought.

[10] While the dinosaur fauna of the lower and middle sections Two Medicine was apparently diverse, the quality of preservation was low and few of these remains can be referred to individual species.

[8] Very few articulated dinosaurs have been found in the formation; most specimens are isolated, bone bed, poorly preserved or broken remains.

[15] No ecological barriers have been postulated apart from upland/lowland habitat preference differences between the Two Medicine and Judith River Formation.

[39] Varricchio observes that during the late Campanian, Alberta and Montana had very similar theropods despite significant differences in the types of herbivorous dinosaur faunas.

The species Piksi barbarulna was described based on forelimb bones from the Two Medicine Formation; it was initially thought to be a bird, but subsequently it was reinterpreted as a pterosaur, likely a member of Ornithocheiroidea.