The title is a play on the phrase "house wrecker," someone whose affair with a married person results in the breakup of that marriage.
Scouting out a new home, Hubie calls over Bertie, who begins to gaze into it before Hubie slaps Bertie to make him realize that before they can move in, the cat (Claude Cat, who has an award for Best Mouser - 1948 along with other then-recent mouser awards), must be removed first. Realizing that the task will not be easy, Hubie comes up with several ways to chase Claude out, all of which are designed to drive him crazy, having Bertie do each of the tricks. First, Hubie lowers Bertie down the chimney on a fishing line. At the bottom of the chimney, Bertie grabs a piece of wood, smacks Claude in the head with it, and is then quickly yanked back up the chimney. When Claude just goes back to sleep, unable to figure out what happens, Bertie is lowered again, pumping air into Claude Cat. When Bertie is yanked back up the chimney and the pump is released, Claude ends up flying all over the living room, hitting all of the walls and ceiling before landing hard on the pillow on which he was resting. Claude then takes the bottle of catnip he had hidden in an overhead lamp and tosses it out the window. With the logs removed from the fireplace, Hubie lowers Bertie and a dog (resembling Hector the Bulldog) in a doghouse down the chimney. While the dog is sleeping, Bertie pulls out the dog's lower lip such that it snaps back on him, but not before Bertie is pulled back up the chimney. Seeing only Claude, the dog viciously beats up Claude before returning to the doghouse, with the doghouse then yanked up the chimney. Completely nerve-wracked as a result of the beating, Claude then runs to the bathroom to take a dose of nerve tonic. While Claude is in the bathroom, Bertie then inserts a lit firecracker into Claude's pillow, which blows up not after he returns to it. Claude then nervously gulps down the remainder of the nerve tonic. Next, Bertie returns down the chimney and runs a piece of string throughout the house, out of it into a water catch drain, down a ladder, and then back into the house, with the other end of the string attached to a rock on top of the chimney. Once Bertie ties the end of the string to Claude's tail, Hubie tosses the rock down the other side of the chimney, which sends Claude flying throughout the house, out of it and back into it, and eventually slamming him into a trash can lid, which begins to drive Claude crazy. Claude then reads "Psychology of Dreams" by Sigmund Fried for advice on dealing with what Claude thinks are bad dreams. When Claude falls asleep, Bertie places earmuffs over his ears, while Hubie and Bertie work on nailing everything that would be in front of Claude that was on the floor in the living room to the ceiling, and painting the ceiling like the floor and vice versa. When Claude wakes up, he sees this and thinks he is on the ceiling (when he is really on the floor) and jumps up to what he thinks is the floor (which is really the ceiling). Claude is surprised when he grabs a bottle of nerve tonic, only to open it and see it "rise" to the floor. Claude then becomes confused when he enters into the kitchen, where everything is still right-side up. Further driving Claude mad is when he looks out one window where an illusion is given to make Claude think he is upside down, and then looks out another to make him think he is sideways, and then out a third to make him believe that the house is under water. Finally broken, Claude runs, screaming, out the house into a nearby tree, where he hides. Having accomplished their mission, Hubie and Bertie return down the fireplace, and roast cheese over an open fire as the cartoon fades out.
- VHS - Looney Tunes: The Collectors Edition, Vol. 6: Supporting Players
- DVD - Looney Tunes Golden Collection: Volume 2, Disc Two
- DVD - Warner Bros. Home Entertainment Academy Awards Animation Collection, Disc 2
- Blu-Ray, DVD - Looney Tunes Mouse Chronicles: The Chuck Jones Collection, Disc 2
- On The Merrie Melodies Show (syndication and FOX), the part where Claude is beaten up by the bulldog is shortened.
- Along with the above edit, the version that aired on ABC.'s The Bugs Bunny and Tweety Show the part where Claude is caught in a firecracker explosion and heavily drinks from a bottle of nerve tonic was cut. Also missing is at the beginning where Bertie plummets Claude in the head with a piece of firewood.
- In the original uncut version, Hubie and Bertie string a rope so that a boulder pushed down the house's chimney will send Claude careening all through the house In this scene, CBS only showed the path of the rope and the end result of Claude completely flattened, not the part where Clause is sent careening all through the house after the trap is triggered. Moreover, this cartoon was cut to end before the final shot, of the mice triumphantly toasting cheese in the fireplace.
- In the last scene where Hubie and Bertie toast cheese in the fireplace, there is an overlap of end music and dialogue followed by an abrupt black-out. This has appeared in all prints (theatrical and television), prompting the possibility that a scene was edited before it was released to theaters.  According to Greg Ford on the commentary found on Looney Tunes Golden Collection: Volume 2, there was another ending where Claude came back down the chimney, landed in the fireplace, got set on fire and "shot out of the chimney."
- First appearance of the redesigned Claude Cat.
- Mel Blanc voices Bertie and an uncredited Stan Freberg voices Hubie.
- "Mouse Wreckers" was nominated for an Academy Award for Best Animated Short Film for 1949, but lost to "The Little Orphan", a Tom and Jerry cartoon.
- The cartoon was loosely remade twice as "Gopher Broke" in 1958, and later as the Tom and Jerry cartoon "The Year of the Mouse" in 1965.
- When Claude was wiggling his mouth, his hand was yellow instead of white.