After the confrontation with David, when Joel grabs Ellie to make her stop you can hear the machete clinking various times as it falls flat on the ground. At the end of the cinematic the machete is shown as if nailed almost vertically on the ground or David's body.
At the University of Eastern Colorado, in the science lab when you enter the room containing monkeys, you open the door into the room. However, after you listen to the dead Firefly's recording, come under attack and exit, that door is now opened out from that room.
The only vehicles shown within Fedra are war vehicles, operated by soldiers. Ellie should not know how to drive a car growing up there.
The truck that Bill helps Joel and Ellie get has an automatic transmission. The battery is dead and they push start it. You can't push start an automatic, only a manual transmission can be push started.
Clickers and Bloaters are explicitly said to use "echolocation" in order to see, but in game-play they actually don't sense people or seem to be aware of their surroundings unless a noise is made. In real life, echolocation works by bouncing your own sound waves off of objects to determine their location when the waves come back to you; meaning that it doesn't matter whether the object itself is making noise. What the Infected have is more like simply a heightened sense of hearing than actual echolocation.
During the climax of the University sequence, Joel is impaled on a rebar after falling from the hospital's mezzanine while fighting a Hunter mook. Ellie removes Joel from the rebar soon after and they successfully escape the enemy assault, without paying the puncture wound any mind whatsoever. In real life, Joel would have almost certainly bled to death within minutes of being disimpaled.
There is actually no scientific way to make a vaccine for a fungal infection. Meaning that there is no need for any of the plot to happen as there is no way to make the vaccine anyways.
Joel recovers from what appears to be months of fragile bed-rest after a single injection of antibiotics. Realistically, he'd need several weeks of physical therapy before he could accomplish what he does in game a few hours later.
When Joel and Ellie find the arcade cabinet in the old pizzeria, the room is reflected in the cabinet's screen, but Joel and Ellie are not.
During the prologue, if Sarah looks in her mirror, her reflection does not cast a shadow.
Gas expires in a matter of months. After 20 years, untreated gas would not be usable in the vehicles the characters commandeer.
A car's engine can be started by putting it on first with the clutch on, switching the key to the "on" position, pushing it to a human running speed, then releasing the clutch. In the game, the sound of the starter motor solenoid is used, which is incorrect when performing this maneuver.
Lincoln High School in the game is modeled and named after Lincoln High School in Lincoln, Rhode Island, despite the location being set in Lincoln, Massachusetts.
During most of the game, Joel has to craft shivs that have limited uses and break. However, while playing as Ellie the player has a knife with unlimited uses. While this makes sense from a gameplay perspective, it makes no logical sense that Joel couldn't find a knife of his own.
A character siphons gasoline out of a truck's tank. However the siphon's outer end is held higher than the gas level (and the tank's opening) which would stop the siphoning. After that, the siphon is left hanging from the tank without purging, which would actually spill the gasoline.
When Joel takes over the sniper rifle, his partners start running towards him without really knowing he has it now. The player can see that because they hide behind a car, visible to the sniper.
In the Firefly hospital at the end of the game it's possible to hear one Firefly tell another that the smuggler (Joel) bought the girl (Ellie) all the way from Pittsburgh. Joel and Ellie's journey started in Boston and while they did go through Pittsburgh the Fireflies can't know that as Joel doesn't mention it and Ellie has been unconscious since arriving.
In the prologue, after Tommy saves Joel from a runner using a brick, Joel hands Tommy his revolver barrel-first.
When Bill and Joel are gearing up for the trip to the school, Bill loads his shotgun, cocks it, then drops it on the table, facing directly toward Joel.
Averted in the scene where Ellie gets her pistol, demonstrating good trigger discipline - only to go right back into the trope when you notice both Joel and Ellie keep at least one of their sidearms in their pants.