The story continues where Diablo II ended. Two of the three Prime Evils, Mephisto and Diablo, have been defeated and their Soulstones have been destroyed, preventing their return. However, the narrator Marius was tricked into surrendering the last Soulstone to a false Archangel Tyrael which was revealed to be Baal, the third brother and last remaining Prime Evil. Marius was subsequently murdered.

Baal is leading an invasion against the northern barbarian lands. His first attack, against the city of Sescheron, capital city of the Barbarian homelands, leads to the stage where Diablo II: Lord of Destruction is set: Harrogath. Situated at the base of Mount Arreat, it is home to the humans who are sworn protectors of the mountain. Baal is currently besieging the city and destroying any settlements along the way towards the mountain's summit.

Baal, the Lord of Destruction, is seeking the Worldstone, a massive crystal of great energies, built to prevent the High Heavens and Burning Hells from consuming the mortal realm completely into their respective folds. It is the source of all the Soulstones and their powers, so Baal wishes to obtain it, corrupt it and complete his brothers' plan to conquer the mortal realm and use it as a staging area to besiege the Heavens in the endless war between the two.

--New features--

A fifth act taking place in and around Mount Arreat in the northern Barbarian Highlands, with an additional act boss, Baal.

Ethereal items: These items do not fully exist in the mortal plane and appear translucent to the human eye. Because of this, they cannot be repaired and will eventually "deteriorate," so to say, so you cannot use them anymore, but they also have better characteristics and lower requirements than their repairable equivalents. However, some magical ethereal items are self-repairing, and some have sockets, and can be made indestructable by inserting a certain rune.

Runes: stones that give powerful attributes to a socketed item when placed in it or even more powerful bonuses when placed in a certain order forming a "runeword" (see Rune Words section below for more information).

Jewels: items serving a similar purpose to gems in that they can be placed in socketed items, but which have random characteristics as opposed to the set characteristics of gems and runes.

Charms: items giving boosts to character's stats when kept in the inventory of the player.

Two new character classes: the Assassin and the Druid.

An expanded private stash for storing items (double the size of the Diablo II stash).

An alternate mainhand/offhand setup that can be switched between via a hotkey in gameplay.

Hirelings (mercenaries) as well as summons can now follow the player outside of the Act in which they were hired. They can also be equipped with armor, a helm, and a hireling-specific weapon (as well as a shield in one case). Hirelings also gain experience and can be resurrected (for a price proportional to their level) when killed.

Class-specific items: new items that only a specific character class can use. These items often contain class-specific bonuses, often adding additional skill points for that character class.

Elite items: more powerful versions of items following the Normal and Exceptional items.

New unique items, including many Exceptional and Elite Uniques.

New set items, including sets that use Class-specific items (ie. only one character class can complete certain sets).

The game can now be played at 800x600 resolution, up from the standard 640x480.

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