Young Kate Barker is brutalized by her father and older brothers, who rape her. Thirty-five years later, the middle-aged Kate ‘Ma’ Barker, now brutalizes innocent people herself, while indulging her monstrous sexual appetites. She lives by robbing banks with her four sons; the pragmatic Arthur, the sadistic Herman, the bisexual Fred, and the loyal, drug-addicted Lloyd. It all begins in the late 1920s when Ma leaves her husband, George, and her Arkansas home and embarks on her own with her four sons on a robbery-murder spree to make her own fortune, while keeping them under a tight leash.
When Herman and Fred are arrested and imprisoned for petty theft charges, Ma takes over the group and leads Arthur and Lloyd on a bank robbery spree to gain enough money to get her sons out of jail. The gang is joined by a gunman, Kevin Dirkman, who was Fred’s cellmate during his incarceration (and his strongly implied lover). The group is also joined by a local prostitute, Mona Gibson, whom Herman frequented before his imprisonment. The gang resorts to more violent action and robberies.
While hiding out at a cabin in Kentucky, Lloyd comes across a young woman swimming at a nearby lake whom he sexually assaults. Not wanting the woman to report them to the police, the Barkers hold her captive and Ma eventually kills her by drowning her, despite the protests of her sons.
Some time later, the gang arrives in Tennessee where they abduct a wealthy businessman, Sam Pendlebury. Holding him for a $300,000 ransom, the sons, particularly Herman, bond with their captive whom they see as the sympathetic father figure they never had. When Herman and Mona go to collect the ransom, they are chased by a pair of FBI agents and barely escape. When they find that the ransom is only half of what they originally demanded, Ma orders her sons to kill Sam rather than let him go. But none of them can bring themselves to do it and they set him free, lying to Ma about killing him.
Next, the gang hides out in Florida Everglades where Lloyd soon dies from a morphine overdose and Mona leaves Herman and the gang after she reveals that she’s pregnant and does not want to be around them anymore out of fear for the safety of her unborn child, which Herman fathered. Her fears are justified when Herman and Kevin give away their hiding place a little later. A local handyman and caretaker, Moses, witnesses them shooting an alligator out on a lake with a Tommy gun and calls the police to report his suspicions.
At the climax, several FBI agents and local police arrive at the Barkers’ farmhouse hideout and a huge shootout ensues between the authorities and the surviving members of the gang. Kevin, Fred, and Arthur are all killed. Herman commits suicide to prevent himself from being sent to prison again. Ma is the last one to fall.