In the level "Bomber", the player take the role of technical sergeant James Doyle aboard a British B-17F. In this role, the player must man the dorsal, tail and port waist guns of the B-17 at various appointed times to fend off attacking German BF109s after the tail gunner "Angus", left waist gunner "Danny", and the radio operator whose name isn't mentioned, are killed; first with the aid of Spitfire fighter cover, then without. The player is also tasked with shutting off the fuel lines to put out engine fires, and cranking open jammed bomb bay doors. Throughout this mission, several B-17s in the squadron are shot down, and the player's B-17 takes a terrible beating from flak and fighter attacks, with substantial battle damage accumulating on the Flying Fortress and its crew. Eventually, the player's B-17 gets ripped in half, and the player must bail out to end the mission.
In Call of Duty: World at War, B-17s appear in the Japanese campaign during the mission "Hard Landing". After the player acquires the M2 Flamethrower and successfully destroys and exits the Japanese pillbox, numerous B-17s can be seen flying high overhead. One unlucky B-17 that has been stricken by Japanese anti-aircraft fire flies directly over the player, clips a palm tree, and crashes into the nearby airfield. The crashed B-17 can later be seen up close when the player's squad arrives at the airfield to fight the occupying Japanese force. The B-17 was originally going to be a fourth killstreak featured in multiplayer, but this idea was later scrapped, along with the other fourth killstreaks. The B-17 in the crash site seems to wear the RAF Coastal Command colors from United Offensive.
The B-17G variant appears in Call of Duty: WWII multiplayer as the Ball Turret Gunner Scorestreak. If the scorestreak is called in by a player on the Axis Powers team, a Luftwaffe Balkenkruez will be marked on the corner of the ball turret.