A major focus of games in the Galactic Civilizations series is the artificial intelligence of its opponents, due in part to the deliberate omission of multiplayer in favor of the single player experience. The game is not easy - the maximum level of skill ("intelligent") is two levels above "normal", which typically takes most first-time players several games to master. Even higher levels of difficulty (in which the computer players receive bonuses to their production and economy) are available should these prove insufficient. Conversely, at the lowest levels of difficulty the AI is severely crippled due to supply shortages.

The AI also makes use of technological developments to design ships of its own. At higher difficulty levels these ships are tailored to the opposition, so players sending fleets of laser-armed ships may find them repulsed by shielded defenders, while those preferring to employ mass drivers will find that they come up against heavily-armored opposition instead.