West reportedly wrote the original screenplay, with Fields contributing one extended scene set in a bar. Universal decided to give the stars equal screenplay credit, perhaps to avoid the appearance of favoritism, but the move incensed West, who declined to re-team with Fields afterwards. The stars spoofed themselves and the Western genre, with West providing a series of her trademark double entendres.
In the American Old West of the 1880s, Miss Flower Belle Lee (Mae West), a singer from Chicago, is on her way to visit relatives. While she is traveling on a stagecoach with three men and a woman named Mrs. Gideon (Margaret Hamilton), the town gossip and busybody, a masked bandit on horseback holds up the stage for its shipment of gold and orders the passengers to step out.
The masked bandit immediately takes an interest in the saucy blonde. As he makes his getaway with the gold, he takes her with him. Upon reaching the town of Little Bend, the others report the robbery and kidnapping to the sheriff (William B. Davidson). Flower Belle then walks into town, unharmed, and explains, "I was in a tight spot but I managed to wriggle out of it."
Later that evening, at the home of her Aunt Lou (Ruth Donnelly) and Uncle John (Willard Robertson), the masked bandit enters Flower Belle's second floor bedroom and they start kissing. However, his presence and departure is witnessed by Mrs. Gideon. She quickly reports what she has seen and Flower Belle angrily finds herself hauled up before the judge (Addison Richards). Offended by her indifferent manner, the judge asks angrily "Young lady, are you trying to show contempt for this court?" She answers: "No, I'm doing my best to hide it!" Flower Belle is then run out of Little Bend.
She boards a train to Greasewood City. It makes an unscheduled stop to pick up con-man Cuthbert J. Twillie (W. C. Fields). When hostile Indians attack, Flower Belle saunters to a window and mows them down with two pistols, while Twillie dodges flying arrows and fights off the Indians with a child's slingshot. Flower Belle has little use for Twillie until she sees a stash of money in his bag. Believing him to be rich, she then plays up to him and they get acquainted. They have an impromptu wedding, officiated over by a passenger, Amos Budge (Donald Meek), a gambler who looks like a minister.
As she has only pretended to marry Twillie for "respectability", Flower Belle gets a separate hotel room in Greasewood City. Meanwhile, Twillie is made sheriff by the saloon owner and town boss Jeff Badger (Joseph Calleia), who has an ulterior motive: he hopes the new sheriff, who is clearly incompetent, will be unable to interfere with Badger's crimes. Flower Belle attracts the attention of Badger, newspaper editor Wayne Carter (Dick Foran), and every other man in town. While keeping her troublesome "husband" out of reach and out of trouble, Flower Belle encounters the masked bandit again. At one point, she kisses Badger, and recognizes that Badger is the masked bandit, musing: "That man's kiss is like a signature."
Twillie attempts to consummate his "marriage" with Flower Belle, but she escapes and leaves a goat in their bed. Twillie, unaware of the substitution, attempts to make love to the goat, and is surprised when he discovers that it is, in fact, not Flower Belle.
One night, Twillie again attempts to consummate his "marriage" by entering Flower Belle's room disguised as the masked bandit. He is caught, accused of being the masked bandit, and is about to be hanged. With the noose around his neck, he makes his last request to the lynching party. "I'd like to see Paris before I die. Philadelphia will do!"
However, Flower Belle saves Twillie.
Frank S. Nugent reviewed the film negatively for The New York Times, writing that "the film is at low tide most of the time in the quality of its humor, in the broad treatment its players and directors have given it, in the caliber of the audience it seems intended to please and in the generally bad odor it exudes." Variety wrote that the film "has its sagging moments, and the slim basic story cannot be taken seriously at any point. But there's sufficient broad humor and elemental comedy to satisfy generally." Harrison's Reports wrote that West and Fields "play up to each other very well and make a good team. Due to their efforts the picture offers good mass entertainment, in spite of the fact that the story is thin." Film Daily wrote that it was "all lusty fun" with "some amusing gags and situations." John Mosher of The New Yorker called West "as fresh and ebullient as ever" after her two-year absence from the screen.
My Little Chickadee was a box office success, earning $2 million in gross receipts.In Matthew Reilly's Shane Schofield series, Gina "Mother" Newman often protectively refers to Elizabeth Gant, as her "little chickadee".