At the reading of the will of Patrick Dennis' father, Mr. Babcock reveals that Patrick is to be left in the care of his aunt Mame Dennis and his nanny, Agnes Gooch. Mame hopes to fill the boy’s life with adventure, but when Babcock discovers she has enrolled Patrick in a non-traditional school, the child is taken from Mame’s custody. Simultaneously, the stock market crash leaves Mame penniless, yet she fights to keep her home intact.
To lift everyone’s spirits, Mame’s friend and fellow actress Vera Charles offers her a small role in a new show as “The Man in the Moon.” Mame flubs her one line, turning the production into a disaster and straining their friendship, though Patrick reassures his aunt that he still loves her.
Desperation drives Mame to a department store job, where she meets Beauregard Jackson Pickett Burnside. In a bid to close a sale, she tries to push a pair of roller skates but cannot complete a cash order and is fired. Back home, she tries to brighten the mood by decorating the house for Christmas and handing out gifts early, even as her hired help struggles to pay the butcher until September.
Burnside arrives at her door, invites everyone to dinner, and is soon seen as Santa Claus by the household—though Mame quips that Santa is more like Rhett Butler. They fall in love and relocate to his family plantation in Peckerwood, Georgia. At first, Burnside’s relatives resist a Yankee wife, but when Mame captures a fox during a hunt, they sing her praises.
The couple embarks on an extended honeymoon around the world, while Patrick matures from a bright, if imperfect, boy into a high school senior who begins to struggle with his grades. Tragedy strikes when Burnside dies in an avalanche, and Mame returns home to find an adult Patrick dating a snobbish, conservative girl named Gloria Upson.
Over drinks with Vera, the two trade sharp, humorous barbs—though they insist their exchanges aren’t born of hatred, but the candid honesty of Bosom Buddies. Agnes, listening in, admits she’s never had a date. Mame and Vera decide to give the uptight Agnes a makeover and send her out to live life, and six months later Agnes returns home, pregnant, recounting her adventures.
Mame later visits the Upsons in Connecticut and learns that Patrick and Gloria are engaged. She finds the Upsons insufferable and bigoted, and is asked to help buy a piece of property next door so Patrick and Gloria can live there “away from the wrong kind of people.” Mame speaks frankly with Patrick about her views, and he admits he’s ashamed of her and her free-spirited circle. A heartbroken Mame wonders what she did wrong raising him.
The two reconcile on a night when they’re dressed for company, the Upsons arriving to judge them. Patrick meets Mame’s new maid, Pegeen, and Mame reveals she has bought the neighboring property to fund the Beauregard Burnside Memorial Home For Single Mothers. The Upsons storm out, furious that Mame isn’t “one of us,” and Patrick, deeply upset, leaves as well.
Years pass, and after World War II, Patrick and Pegeen are married with a child, Peter. Mame, preparing for a trip to Siberia, asks that Peter come along. As they board the plane, Patrick notes that Mame hasn’t changed, and mother and son wave goodbye as they head toward a new horizon.
