The short features Tom the cat and Jerry the mouse chasing each other in a pseudo-warfare style, and makes numerous references to World War II technology such as jeeps and dive bombers. The Yankee Doodle Mouse won the 1943 Academy Award for Best Animated Short Film, making it the first of seven Tom and Jerry cartoons to receive this distinction.
Tom pursues Jerry through a cellar, but the mouse successfully dives into his mousehole. Tom peers into the hole, and Jerry launches a tomato from a mousetrap into his face. Jerry then climbs up the wall and grabs a handful of eggs from a carton marked "Hen-Grenades". As Tom wipes the tomato off his face, he is promptly covered in egg, with one hit to the eye leaving the effect of him wearing a monocle. Jerry shoots off the corks from a champagne case, knocking Tom into a tub of water with only a pot to keep him afloat. The mouse promptly launches a brick from a spatula, sinking both the pot and Tom. Leading to the 1st war communiqué message, it reads "Sighted cat – sank same. Signed, Lt. Jerry Mouse."
Later, Tom approaches Jerry's mousehole with a cheese and a mallet in his hand, while Jerry uses a pipe as a makeshift periscope to observe; spotting this trap, Jerry instead opens the ironing board cupboard, sending the board crashing onto Tom's head. Jerry charges down the board on a jeep made from a cheese grater attached to a roller skate, tearing Tom's fur as he speeds past twice, after which the jeep crashes into a wall, sending a sack of flour tumbling down. Adapting quickly to the situation, Jerry grabs the sack and spreads a makeshift flour smokescreen, which blocks Tom's vision but not Jerry's. He smacks the nearly blind Tom in the rear with a board three times, but eventually Tom falls to the ground facing the mouse; Jerry slaps Tom a fourth time before the cat can do anything and then runs for it. The sequence then end with an strange fade out.
Tom, now wearing a bowl as a helmet, throws a stick of dynamite towards Jerry, who immediately throws it back to Tom; this continues until Jerry performs reverse psychology by taking it from Tom, provoking the cat to steal it back and this new cycle to continue until Jerry leaves Tom to witlessly hold the stick, which blows up as soon as the fuse goes off. Jerry jumps into a tea kettle to escape the cat's wrath, but Tom sees him and throws another firecracker into the kettle; Jerry panics, but the oxygen has run out and the mouse escapes through the spout with no explosion. The puzzled cat opens the kettle's lid and sticks his entire head in just as the firecracker goes off, leaving him resembling a blackfaced sunflower.
Continuing his attempts to blow up the mouse, Tom launches a paper airplane with a firecracker hidden on top, but Jerry blows it back beneath Tom, who barely spots the firecracker before it goes off and is again black in the face. Jerry then plants an enormous stick of dynamite behind Tom; the cat sees it and screams in terror until the cracker splits into successively smaller sticks reminiscent of matryoshka dolls, ending with a minuscule replica of the original firecracker. Tom laughs, believing this to be harmless, but the dynamite explodes powerfully.
Jerry then goes through a hole in a barrel and jumps into a makeshift plane fashioned from an egg carton (launched from a slingshot made from a rubber band). He drops a succession of light bulbs, one of which hits Tom's head, and a banana bomb, which hits Tom's face. Tom grabs a Roman candle and skillfully shoots down Jerry's now weaponless plane, piece by piece. Jerry uses a brassiere to parachute from the plane, but is again shot down by Tom. Jerry races into his mousehole to escape, but Tom pushes another Roman candle into the hole and fires off six shots.
The fireballs pursue Jerry through the mouse hole through the barrel going back and forth until he eventually he leads them into a hose, which he shoots like a machine gun into a barrel where Tom is hiding. The barrel explodes, leaving Tom riding the remaining parts of the barrel like a bicycle, which then crashes into the wall. Recovering, Tom fires a dart gun at Jerry, which hits him on the tail as he again attempts to dive into his mousehole.
Tom grabs Jerry and ties him to an ignited rocket; Jerry pretends to help himself be tied up, but unknown to Tom, he is actually strapping his own hands to the rocket. Jerry emerges from the ropes, and the puzzled Tom does not realize what has happened until Jerry waves at him. Tom tries to blow out the fuse, but the rocket shoots high into the sky and explodes. The explosion forms the Stars and Stripes. Jerry proudly salutes the flag, and a final war communiqué is displayed, which reads "SEND MORE CATS!" Signed, Lt. Jerry Mouse.William Hanna as Tom (uncredited)
The short was reissued in 1950s. A gag, involving ration stamp was removed. In the reissue print. In the sequence where Jerry hit Tom with a board four times, as Jerry attempts to run off the sequence fades to black. In the original missing sequence, Tom is supposed to follow him only to get his head stuck in Jerry’s hole. Jerry then use Tom’s tongue to lick a war bond stamp. The second war communique which reads: "Enemy gets in a few good licks".