Continuity mistake: It was briefly stated in the second film that the T-Virus was created by Dr. Ashford to cure his daughter Angela and that the Red and White Queens were based on her. This movie contradicts that by suggesting that Dr. Marcus created the T-Virus to cure his daughter Alicia, and that the Red/White Queens were modeled after her. While the rest of the movie stays true to the continuity of the previous films, this rather obvious ret-con is still a major continuity gaff.
Continuity mistake: When the Senator is about to be sacrificed, the cloth on her mouth immediately disappears for a split second. (01:29:35)
Continuity mistake: Periodically, we see beyond the wall, where it appears to be heavily forested just beyond the wall and a distance beyond. However, once past the wall, the group starts with a cliff down and then it is completely barren, with completely different weather conditions (frequent red rain).
Continuity mistake: At the end of the movie when the mothership takes off the central saucer section is in place, yet we saw the queen alien fly off in it earlier on.
Continuity mistake: Michelle ends the phonecall in her car at 6:27pm. When she regains consciousness in the bunker it's 6:29pm. Either she was retrieved from her crashed car, taken to the bunker, chained up and hooked to an IV in 2 minutes (impossible), or she's been unconscious for exactly 24 hours, which would be a sign of a serious brain injury (with no other symptoms). Either way something's not right.
Continuity mistake: Throughout the movie, fire axes seem to be the weapons of choice. Only two fire axes are used, but they appear recurrently. In the very first use, the protagonists grab fire axes to butcher the monster called Beverly. Blood and gore go everywhere; yet, the axes emerge from this bloodbath with no blood or gore on the handles - they're virtually pristine moments later. The axes are used again and again, right up to the ending, and blood comes and goes from the axe handles seemingly at random.
Continuity mistake: When they are at Sarah's house, the boy's father tells her to go outside and ask Lucas to pull the van around back. When Sarah walks to talk to Lucas her long braided hair is tucked into her shirt and her arms are crossed. In the next shot when the camera comes back, her hair is on the outside of her shirt despite her arms still being crossed. (00:45:55)
Continuity mistake: The gang Bo is reluctantly part of gets to Maurice's crib where he is playing cards with his homies. The red jacketed one is defiant, and grabs a handful of red and blue chips in front of him tossing them in Angelo's face. But if you check out of the table in the wide shots before this occurs, you'll notice that red chips were never in the stack in front of him to begin with. (00:19:05)