The story line of Diablo III is mostly unknown to us at this point. We know it takes place twenty years after a few powerful heroes saved Sanctuary from the demonic onslaught in Diablo II.
Contents
Known Story
The demonic invasion 20 years ago affected very few people, most of which have been wiped from the face of Sanctuary. Many of the few survivors went mad from their experiences. Some people know that some sort of conflict took place, but for the most part the war against Diablo is a myth.
What happened to Tyrael after he destroyed the Worldstone is unknown to everyone. Scholars like Deckard Cain anticipated a huge invasion of demonic forces as the protection from the High Heavens and the Burning Hells, but no invasion have begun. Cain has spent the last years trying to figure out what happened, and trying to prepare us for the inevitable onslaught.
We know from the Diablo III cinematic that a great comet of some importance is falling down on to the Tristram Cathedral, and that some unlucky soul (if it's Leah or Cain isn't sure) is hit by it. Hell's armies are amassing, and it isn't safe any more.
Characters
All NPCs, many monsters, and the player characters in the game all have in common they are characters, meaning they play a part of the story, and are joined with characters from lore such as the manuals, the novels or comics. Anything that is canon and some that is not can be found in the character category:
Monsters
Sanctuary Literature
Besides the novels and such books, there are also books created in Sanctuary. Everything from journals of important characters, to full literary works and prophecies. It's all part of the world, and is added to the Diablo database:
Artefacts
Certain pieces of equipment, jewellery, weapons or other items contain so much power they are called artefacts. The world of Diablo is full of them, and if you're lucky you can find some powerful artefacts in your travels around Sanctuary.