The Ancients are depicted as godlike beings that existed on Earth before humanity. The three Ancients that Pious may align with were expelled from this universe, and Pious works to bring about the return of his Ancient. The featured Ancients are:
A fifth alignment, colored yellow, was confirmed by Denis Dyack to be the alignment of another Ancient that was not included in the game. In-game, yellow appears on unaligned runes, disintegrating enemies, the magick that afflicts Anthony, and a trap that covers the floor in certain areas.
The Ancients are based on the 'Great Old Ones' which appear in H.P. Lovecraft's Cthulhu-Mythos.
Also like the Great Old Ones in H.P. Lovecraft's Cthulhu-Mythos, the Ancients are not supernatural gods, but alien beings that arrived on Earth eons ago. A mural discovered in Edwin Lindsey's chapter shows Mantorok appearing before the Khmer people after a celestial object impacts Earth (it is not known whether this was a spaceship or meteor/asteroid). In a later mural, the Khmer are celebrating Mantorok's benevolence while three flying saucers fly overhead.
- Coincidentally, the Ancients voice actors also voice some of the chosen characters in the Tome of Eternal Darkness:
- Ulyaoth and Pious Augustus were both voiced by Richard Doyle.
- Chattur'gha and Michael Edwards were both voiced by Greg Eagles
- Xel'lotath shared the same voice actresses as Alexandra Roivas and Ellia (Jennifer Hale and Kim Mai Guest, respectively).