Master of Orion II won the Origins Award for Best Fantasy or Science Fiction Computer Game of 1996, and was well received by critics, although reviewers differed about which aspects they liked and disliked.

Long before the time in which the game is set, two extremely powerful races, the Orions and the Antarans, fought a war that devastated most of the galaxy.

The victorious Orions, rather than exterminate the Antarans, imprisoned them in a pocket dimension before departing the galaxy, leaving behind a very powerful robotic warship, the Guardian, to protect their homeworld.

[2]: iv Some time after the game starts, the Antarans, having broken out of their prison dimension, begin to send increasingly powerful fleets against the players' colonies, to destroy them along with any defending ships, before they disappear back to their mysterious realm.

There are three routes to victory: conquer all opponents; be elected as the supreme leader of the galaxy; or make a successful assault against the Antaran homeworld.

[6]: 16  Dictatorships are the most common governments for the pre-defined races,[6]: 13–15  costing no picks while providing appropriately minor bonuses and penalties.

Unification governments provide advantages in farming and industrial output and defense against espionage, but do not benefit from morale and assimilate conquered aliens at the slowest rate.

[2]: 47–52  The most desirable systems are usually guarded by space monsters, much less powerful than Orion's Guardian but still a challenge in the early game, when fleets are small and of low technology.

[2]: 75  However, a single hostile warship of any size can blockade an entire system, preventing the delivery of food and halving the colonies' outputs of farming and industry.

[2]: 137  Players can use surplus money to accelerate industrial production at specified colonies, but not to increase agricultural or research output.

This limits the size of empires' fleets in the early game, where one can add only one frigate (smallest type of ship) per additional starbase or one battleship (largest type of ship in the early game) per four new starbases without causing the "command rating" to go negative, which is very expensive.

[2]: 64–65  Players can also acquire technologies by exchange or diplomatic threats, spying,[2]: 142  hiring colonial leaders or ship commanders with knowledge of certain technologies, planetary conquest, dismantling captured enemy ships, random events, or by stumbling upon it in a derelict craft orbiting a newly discovered planet.

[2]: 100–102  Technological advancements also make available modifications for most weapons, which usually entail a significant increase in their cost and size but can greatly improve their effectiveness in the right situations.

[6]: 42–43 Players can design warships, provided they choose the "tactical combat" option in game set-up.

[6]: 118–132  Colonies conquered by Telepathic races, either by Mind Control or ground invasion, are instantly loyal to their new owners.

[6]: 23  Recently occupied colonies by non-Telepaths on the other hand are disaffected, have poor productivity, and may rebel and rejoin the empire which founded them.

[3][9] The first "Orion" game's graphics had also been heavily criticized, and the second included higher-quality artwork displayed at a higher resolution.

[15] Master of Orion II secured 10th place on PC Data's computer game sales chart for the month of November 1996.

[9] Robert Mayer of Strategy Plus argued that the concepts are good but the interface makes it needlessly difficult to access information vital to managing them.

[3] Offering yet another opinion, Next Generation found the difference from Master of Orion to be minor, concluding that "perhaps the biggest problem is that the game is a little too stagnant, and doesn't really break new ground in the now-crowded galactic conquest genre".

[3][12][21][9] Macworld's Michael Gowan wrote that Master of Orion II's "countless strategy options will keep you coming back for more".

[31] The Master of Orion series set a new standard for space-based 4X games, with a retrospective review by Chick describing it as "a towering monolith in the genre that has cast an eight-year-long shadow over everything that's followed... Master of Orion is still the definitive name in space opera games".

One review of Space Empires IV made several comparisons with Master of Orion II, commenting favorably on the complex tactical combat, while criticizing the relatively "sparse graphics and sound", concluding that it was the most sophisticated game available in the genre, but that it built "on the basic foundation of Master of Orion" instead of "breaking new ground".