- Specimen 6 is clearly branded with an identifying number on its forehead, yet none of the other Xenomorphs held at the research facility are marked in such a way.
- During the first level of the Alien campaign, the player can observe Katya sending a distress call to the USCM. However, in this appearance her "aura" is green, indicating she is a human; it should be blue because she is a synthetic.
- The underbarrel grenade launcher on the M41A/2 Pulse Rifle is never reloaded; any additional ammunition collected for it is magically teleported inside the weapons.
- In the level "Refinery" of the Alien campaign, after the player has passed through the generator room and harvested the civilian who is fixing the door, they will find a vent in the ceiling of the hallway outside that is covered by a grate. Hitting this grate with Six's tail causes the grate to fall away, but even though an open vent is seen, it cannot be entered.
- Throughout the game, both Tequila and Katya act as though they can see everything that Rookie sees. However, cutscenes at the beginning and end of the Marine campaign show that Rookie does not have a camera anywhere on his body, so it is not clear how they are receiving this visual information. In fact, none of the Colonial Marines in the game have personal cameras like those in Aliens.
- As with the more recent films featuring the Xenomorph, several characters in the game are impregnated by Facehuggers far more quickly than should be possible; Van Zandt is seemingly implanted with a Chestburster in just a couple of hours, while Tequila is impregnated even more quickly than that — Rookie finds her within an hour after Typhoon is shot down and she is already conscious with a Chestburster inside her. The Abomination is also born incredibly quickly.
- There is a major paradox in the game surrounding events that take place inside the Hive while Rookie and Dark are there, specifically with regards to the death of the Matriarch:
- At the very start of the level "Refinery" in the Predator campaign, Dark sees the fully-grown Abomination, meaning the Matriarch must already be dead at this point (as, according to the Alien campaign, she is killed minutes after Six impregnates Wolf in the ruins, and certainly before the Abomination could be born and grow to maturity). However, later in the same level, Dark overhears a Marine saying that Delta and Echo teams (presumably Van Zandt and his men) are making an assault on the Queen, which does not make sense if she is already dead.
- Later still, near the end of the level, Dark enters the Hive and finds the Matriarch's body. It takes around ten minutes to reach this point following the earlier comments by the Marines. However, Rookie cannot possibly have engaged the Matriarch until several hours at least after Van Zandt's assault has failed, because the Major has been cocooned and impregnated with a Chestburster by the time Rookie reaches him, and this is before Rookie fights the Queen. In the Marine campaign, Tequila confirms that Van Zandt's squad were the last people to enter the Hive prior to Rookie, so the Delta and Echo teams Dark hears mentioned could not refer to anyone else.
- The issue is compounded when considering Rookie's actions before he goes into the Hive. Prior to entering the refinery, he repositions a nearby satellite dish so that it is pointing roughly towards the refinery itself. When Dark comes across the same dish in his campaign, it is still in its original position, meaning Rookie must still be inside the colony or the mines at this point, making it impossible for him to reach the Matriarch in time to kill her before Dark reaches her chamber, especially considering all the things Rookie has to do in between.
- The acid-spitting Runners in the game have distinctive ridged heads, yet when viewed through Dark's Xeno vision mode, they have smooth carapaces, just like the Dragon in Alien3.
- From the level "Jungle" onwards in the Alien campaign, Specimen 6's shadow is that of a Praetorian, despite the fact cutscenes show Six is still just a Warrior for the duration of the playable campaign.
- In the level "Ruins" of the Alien campaign, the player (as Six) works their way through the ruined Yautja temple to a doorway. Comparisons with the same area in the other two campaigns shows that the door Six enters leads to the site where Typhoon crashes (although this has not yet happened at the time Six is there). However, instead of the crash site, Six emerges from the doorway into the combat arena, which is actually at the opposite end of the ruins.
- When Dark enters the Pyramid at the end of the game, he sets an ancient Self-Destruct Device on the sarcophagus of his ancestor before a large stone panel in the floor opens to reveal a lava chamber below, where he fights the Abomination. When Rookie arrives subsequently, there are suddenly railings around the open pit that were not there before, and the Self-Destruct device is missing from the sarcophagus.
- Tequila mispronounces Acheron when referring to the moon from Aliens, saying it with a hard 'ch' sound ("Ackeron") instead of a soft one as it should be.