Some years after Lord British has returned to power, the Avatar is captured and tied on a sacrificial altar, about to be sacrificed by red demon-like creatures, the gargoyles. Three of the Avatar's companions, Shamino, Dupre and Iolo, suddenly appear, save the Avatar and collect the sacred text the gargoyle priest was holding.

The Avatar's party flees through a moongate to Castle Britannia, and three of the gargoyles follow. The game begins with the player fighting the gargoyles in Lord British's throne room. After the battle, the Avatar learns that the shrines of Virtue were captured by the gargoyles and he embarks on a quest to rescue Britannia from the invaders.

It is only later in the game that the Avatar learns that the whole situation looks rather different from the point of view of the gargoyles – indeed, they even have their own system of virtues. The quest for victory over the gargoyles now turns into a quest for peace with them.

The development of the Ultima series originated on the Apple II series and every game thus far had been developed primarily on that platform. However, by 1990, the 8-bit computer market was declining rapidly and the plans for the game had finally outgrown the hardware's capabilities (excluding the 16-bit Apple IIGS, however its market size was too small to justify a port). Ultima VI became the first Ultima game to not be available on Apple II.

It was one of the first major PC games directly targeted to PC systems equipped with VGA graphics and a mouse, when the big gaming computer was still the Amiga. The game supported sound cards for music as well, which were not yet common when it was released. Other sound effects, such as the clashing of swords, magical zaps, or explosions, were still played through the PC speaker. The Amiga version was itself ported from the PC and due to a lack of reprogramming it was very slow and was generally considered unplayable without accelerator card on a first- or second-generation Amiga. The only 8-bit computer system to which the game was ported was the Commodore 64 due the fact that it still had a very sizable market share. The C64 version lacks many features of the PC version, not just in aesthetics (no portraits), but also in gameplay (no horses, no working gems, reduced NPC dialogs, simplified quests etc.); it is generally considered much worse than the earlier C64 Ultimas.

A port of the game for FM Towns platform was made primarily for Japanese market. This CD-ROM-based version included full speech in both English and Japanese. Remarkably, in this particular version voice acting was recorded at Origin, mostly by the people the characters were based on (with Richard Garriott as Lord British, Greg Dykes as Dupre, etc.), though not all personnel could be reached at the time of recording, so some substitutes were used.

The game came with a cloth map of Britannia and a Moonstone made from a black colored bit of glass. Slightly improved versions of the Ultima VI engine were also used for the Worlds of Ultima spin-off series.

The DOS version of Ultima VI may have sound and speed problems when running on modern computers and operating systems. However, it can run reliably in a DOSBox environment. An engine remake project called Nuvie, similar to the goals of xu4, Exult.

Dragon gave the game 5 out of 5 stars, but only 3 out of 5 stars for the Super Nintendo version.

In 1996, Computer Gaming World ranked it as the 44th best game of all time, stating: it "hit new heights in virtuality with the defined objects in the game world" and "also presented a brilliant treatise on the danger of prejudice."

A recreation of Ultima VI using the Dungeon Siege engine, The U6 Project (aka Archon), was released on the 5th July 2010. Another remake project uses the Exult engine, using graphics from Ultima VII. Ultima 6 Online is an MMO version of Ultima VI.