While in Crawford, Lee goes outside to get a battery and jumps a barbed wire fence by jumping off a building only on one side of the fence. This fence is unclimbable and it's impossible to return that way. Lee gets out the first time with the help of Molly and Hilda to reach the rooftops. Lee returns to this spot again to obtain a tape. When he is done lee turns around and walks back and the camera cuts to lee back inside the building. However lee shouldn't have been able to get back, because he can't get back the way he came and he can't climb back to the roof without molly and/or Hilda.
If you refuse to give Irene the gun, when she kills herself and Glenn goes to pick up the gun, the walkers appear from the forest, and even though Carley was given the gun back, Glenn still has the gun in his hand, as if Carley had an extra gun with her.
When checking the fence perimeter in Starved For Help, Lee's axe keeps disappearing and reappearing.
When Lee shoots the undead officer in the head the blood is purple, in the next shot the blood is red.
After Lee gets bitten, he passes out several times as the infection gets worse. Even though in The Walking Dead comics, TV show, and even future installments of this game series, passing out is not shown to be a normal symptom caused by a zombie bite.
The U.S. military did not use the Jeep Wrangler as seen in the game.
Irene wants to kill herself because the walkers "are satanic" and "are not of God" and would rather commit suicide to remain closer with god. However according to the bible, suicide is a sin worthy of being sent to Hell for.
When Lee puts a videotape in the camcorder, the tape is facing the wrong way.
A sign on the abandoned shack near the train track is misspelled ('Tresspassers' will be prosecuted).
Despite being told by Shawn that Clementine is not Lee's daughter, Hershel refers to her as "your daughter", a few seconds later and onward.
In "A New Day" upon hearing Shawns screams Lee decides to run around the house despite being at the barn door as the scream took place and would be able to see Shawn and could run straight towards him, instead he chooses to waste time and rush around the building.
If you choose to give clementine the jumper at the end of episode 2, She will wear it during episode 3, however later on at the start of episode 4 during the episode 3 summary, clementine is shown without her jumper on.
Clementine should not have been strong enough to drag lee indoors after he passed out in the streets. Not even to mention, the zombies should have noticed and tried to eat her.