A newspaperman jumps in the river to drown himself. He reappears as a cockroach, who finds he can still type by jumping up and down on the keys of a typewriter. He is in love with Mehitabel, the office cat. He writes poetry to her, and tries to keep her on the straight and narrow. Big Bill the Alley tom cat is Mehit's heart-throb, and Archy's nemesis. She has kittens, and archy declares war in a George Herriman sequence.

In New York City, a poet commits suicide by jumping off a bridge, and to his dismay, is reincarnated as a cockroach named Archy. Realizing that as a cockroach, he is acquainted with all the little insects and animals that he never knew before, Archy feel comfortable with his life in Shinbone Alley, his new neighborhood. A philosophical fellow, Archy concludes that he has been "transmigrated" into a cockroach and that he used to be a poet who felt like a cockroach, and now is a cockroach who feels like a poet. After entering a newspaper office one night, Archy begins to type a message on the typewriter by jumping from key to key, which amuses his insect friends. Because he is unable to work the shift key, his missive is entirely in lowercase letters, but his words reflect the observations of a deep thinker. He asks the reporter who uses the typewriter by day to put paper in the typewriter every night and leave apple peelings for him to eat, offering in exchange to type exclusive stories about his back alley world. For his efforts, Archy says, he needs neither credit nor salary, but only the right to create his "immortal poetry." An important alliance is thus formed, the first in newspaper history, between the cockroach and the reporter, as Archy writes about the city from its underside. One of the stories he writes about is that of a sexy cat, Mehitabel, whose heart has been broken a thousand times, and who insists she is the reincarnation of Cleopatra. Archy writes that, despite her hard life, she continues to sing and dance " toujours gai ." Sometimes Archy worries that she is too exuberant and should find a job as a well-bred house cat, but Mehitabel finds his morality annoying. When two tomcats, led by a feline named Big Bill, return to Shinbone Alley after being away on the prowl, Bill and Mehitabel resume their once-broken affair. Mehitabel claims she is in love, but Archy thinks she has a predilection for tomcats. For his interfering, Archy is flicked away by the randy couple. While worrying about Mehitabel, Archy pours out his heart in his writings and reports on his brief acquaintance with a moth who fried himself on a lightbulb in order to see the secret heart of a flame. When the abusive Bill breaks up with Mehitabel, she returns to Shinbone Alley the worse for wear, engendering the gossip of the neighborhood felines. Archy tries to reason with Mehitabel, saying that her morals are the "lowest, loosest and limpest," but she counters that she has never claimed to have any. Although Mehitabel reports that she left Bill, Archy doubts that she has ever left a tomcat. When she argues that she left her lover Ralph, Archy reminds her that the cat was dead at the time. Despite her anger, Mehitabel eventually admits that she treats Archy badly, but, in the end, he is always right. She says that although he is an ugly bug and she a glamorous and irresistible cat, they are both "flotsam and jetsam on the sea of life." Archy almost has her convinced to get a job as a house cat, when Tyrone T. Tattersall, an old and frayed-looking impresario cat, comes to the alley and offers to make Mehitabel a star. Although Archy warns that Tattersall is a phony, Mehitabel goes with him, leaving Archy behind. Feeling rejected and suicidal, Archy is almost run over by a car. He writes a letter to his "boss," the reporter, and says goodbye to his friends, Freddy the rat and Harry the tarantula. He then jumps off the window ledge, but flutters safely to the ground. His friends try to help by knocking an ink bottle over on him as he again jumps over the ledge, but, again, the wind gently drops Archy to safety. When he tries to spray himself with pesticide, he accidentally kills George the fly. At a billiards parlor, Archy chases balls in the hope of being crushed, until the players see him and sweep him into a trash can. There he encounters Bill, who starts to bully him, but when Archy begs to be killed, the cat refuses to cooperate. When Bill wonders aloud what has Archy so depressed, the cockroach explains that Mehitabel went off with Tattersall. Meanwhile, Tattersall has taken Mehitabel to a theater to train her in Method acting. Tattersall begins to mistreat Mehitabel, and as Archy and Bill secretly watch, the impresario reminisces about better actors while coaching Mehitabel in Romeo and Juliet . When she performs her lines as a burlesque routine, he is troubled by her amateurish performance and longs to get away from her. He orders her out, but she sends him away instead and then allows Bill to seduce her. Kicked away when he tries to remind Mehitabel about Bill's previous rejections, Archy tries to deny his feelings for her. In a dream, he fantasizes that he starts an insect revolution by declaring war on the human race, delivering rousing speeches to recruit the bugs by reminding them how they have been persecuted. Later, when Mehitabel inevitably returns to Shinbone Alley, she has a litter of kittens. She tries to drown them during a thunderstorm, but, with Archy's unwanted help, saves them. As the north wind blows, Mehitabel reluctantly agrees that it is winter, and following Archy's advice, takes a job as a respectable house cat in a high-rent district. Archy is at first pleased with himself for making Mehitabel respectable and continues to write stories, one of which concerns a lightning bug he meets. However, Mehitabel's life of ease is not to her taste, and although she submits to being fawned over and petted, she longs to claw the furniture. Annoyed that everyone goes to bed at nine o'clock, she struggles to keep her kittens out of trouble. On the pretext of writing a story about life in high society, Archy slips in through the keyhole, but Mehitabel tells him that cockroaches are not allowed in the house, as they are "too middle-class." Before leaving tearfully, he reminds her that he is a cockroach cum laude and has relatives in Buckingham Palace, prompting Mehitabel, for the first time, to feel remorse for hurting another's feelings. Outside in the cold, Archy gets drunk on the dregs of a whisky bottle and considers picking a fight with Bill, but becomes frightened by his own shadow. Stumbling along, he enters a bordello of ladybugs, who try to rob him, but who are disappointed to find that all he has in his pockets are poems about Mehitabel. When he awakens, Bill is there, complaining that Archy has turned Mehitabel into a "pussycat." Admitting that he ruined Mehitabel by taking away her pride, Archy decides that cockroaches should not play with destiny. Archy is longing for the way it used to be, when, to his surprise, Mehitabel, preferring her old life, returns and is welcomed by all the stray cats of Shinbone Alley. Philosophically, Archy says that he cannot blame her for being what she has to be and, glad that she is his friend, admits that she is "just plain wonderful."