Duck and Cover! is set in a region described variously as the Mareseyside Wasteland, Flankashire Wasteland, and Great Braytain. The setting is heavily based on the northwest of England and references the areas around it. Great Braytain is stated to be not part of Equestria, but was still hit by balefire, implying that it was an ally of Equestria, or at least caught in the fallout. Duck and Cover! does not directly reference any other stories, though many references are implied.
The story is told from the perspective of Atom Smasher, a young pegasus mare from Stable 512. This stable was never completed, and lacked many of the conventional trappings of stables, including PipBucks, and a sealed front door. Atom's talent is explosives, and her history in the stable was one of isolation and troublemaking. She leaves the stable out of boredom with only her jumpsuit, a Nerf gun and a piece of junk made to look like a PipBuck.
Atom proceeds to blunder around the wasteland doing whatever amuses her most at the time, which usually revolves around going up to the biggest, meanest threat in the wasteland at the time and removing it from existence with explosions and style. Over her travels, she's joined by a Regulator from Equestria called Full House, a Steel Rangers Scribe called Shooting Stars, a diamond-dog-like coal puppy called Snowy, and a pre-war propaganda poster depicting a caricature of a zebra that she dubs Xena. Her antics get her the praise of Tribute, the DJ and runner of the local radio station, Radio Free Mareseyside, starting with her destruction of the Enclave Thunderhead Majesty over Manechester.
While initially thrilled with her apparent heroism, House and Stars grow weary of Atom's short attention span and total disregard for others in her pursuit of amusement. On their journey they destroy an industrial slave town (much like Fillydelphia); kill the wife of Bravehorse, leader of the barbaric Scolts; get transported to the town of Brumare in an alternate, medieval world, but then return; root out another secret Enclave base in a former stable; break up a match of extreme football, a grisly blood sport run by raiders; meet a band of gryphon mercs trying to gain peaceful entry to the Royal Liverpole Building; and meet up with Tribute and her news assistant Grapevine, based at the top of the Royal Liverpole Building.
In a live interview, Atom casually explains that the Enclave are on their way to bomb Manechester and Liverpole into dust, and the Scolts are coming to invade too. Tribute sends them to a pre-war airbase at Formby to secure the anti-air guns there. A lone-wolf sniper kills Snowy, but they secure the guns. When they get back, they find that the gryphons (on Atom's suggestion that they try something more pragmatic) have forced entry and killed all the residents, and Tribute is missing. In frustration, Atom kills all the gryphons. In disgust, House and Stars abandon Atom.
Atom wanders around for a while doing nothing of importance, until the Steel Rangers abduct her to coerce her into helping them deal with the Enclave. Despite Atom's sociopathy, the general public of the area love her, and formed a militia called the Children of Atom (title taken directly from the Fallout 3 faction) to defend Manechester. On the morning of the invasion, Atom and Grapevine infiltrate the Queen's flagship to plant a beacon on board that the guns at Formby use to take it down. In the ensuing battle of Manechester, Atom orders the destruction of the bridges over the river, trapping the Scolts and raiders and leading them to be massacred by the Enclave, and leads the Enclave into a trap to destroy them with balefire eggs.
The end of the story contains references to four "DLC" packages, Train Simulator 2299, Strictly Come Wasteland, Speed Radiator and Pirates of, Um... Amblesey. It is not known whether these are a throwaway joke, or will actually become short stories in their own right later on.