Mo LoBeau's birth and infancy are a mystery. Eleven years earlier during a hurricane, a man named the Colonel found a newborn strapped to a billboard that was floating down a river. He saved her, named her Moses (Mo) and is raising her, together with Miss Lana. Mo believes someday she'll find her "upstream mother." Although she misses knowing who her real mother is and continues searching for her, Mo considers herself lucky to have been rescued and to be living with the Colonel and Miss Lana.
The Colonel and Miss Lana operate a café in Tupelo Landing, N.C., population 148. The Colonel himself is a mystery because he has no memory of his life prior to finding Mo. He lost his memory when he sustained a head injury when his car crashed the night of the hurricane; he found Mo as he was stumbling away from the wreck.
When a man from town found the two, the Colonel was wearing a colonel's uniform with the name Lobo on it. Miss Lana changed the name to LoBeau when Mo started kindergarten. The Colonel hates lawyers and even has a sign in the café that says, "No Lawyers." He and Miss Lana have a three-day rule — whenever either of them is away more than three days, the one who is away must phone so the other knows they are OK.
Dale Earnhardt Johnson III is Mo's best friend. When Mr. Jesse, a frequent patron of the café, is murdered, Mo and Dale decide to solve the murder. Mo goes to the crime scene and spies on Detective Starr and two deputies, Marla and Ben, who are conducting the investigation. Starr is in the area already because he's been working on a case involving stolen money. Mo trips and falls in the water, which announces her presence to the detective and deputies, and at the same time discovers the murder weapon — a wooden oar belonging to Mr. Jesse's boat.
Dale is a person of interest because he was one of the last to see Mr. Jesse before he died. Starr doesn't think that Dale murdered Mr. Jesse, but he decides to take him into protective custody as a setup to lure the murderer out of hiding. Mo and Dale notice that another man is spying on them. They call him Plainclothes Phil and think perhaps he is acting as a bodyguard for Starr. About the same time, the Colonel leaves, and Mo and Miss Lana begin to worry when he breaks the three-day rule.
At the funeral for Mr. Jesse, the congregation is astonished to learn that the grumpy, churchless Mr. Jesse gave $100 weekly, totaling over time, more than $50,000, to the church.
One night, Mo returns home to find their living area torn up and Miss Lana missing. Dale arrives right behind her and finds a note addressed to Starr on the kitchen table. They deduce that the murderer has taken Miss Lana. Out of fear, they run away from the house, but Starr shows up and sees them fleeing.
Starr's team searches for clues and determines that Miss Lana was dragged away after a struggle. As Mo and Dale look at mug shots on Starr's laptop, Miss Rose stops by to comfort Mo. Suddenly Dale sees Plainclothes Phil's picture. They learn from Starr that Plainclothes Phil is not part of their investigation but that he is Robert Slate, a wanted bank robber who recently escaped from prison.
Mo goes home with Miss Rose and Dale, so she won't be alone. The next day Slate calls, and they learn that he has both the Colonel and Miss Lana and wants a $500,000 ransom, the amount of never-recovered money from Slate's bank robbery. A trace on Mr. Jesse's money to the church reveals that it was from the robbery and that he was connected to the crime.
As Mo and Dale help prepare Miss Rose's house for a forecasted hurricane, Mo gets a call from the Colonel. The connection is poor, and Mo can understand only that he escaped from Slate, that she is to get a packet from his closet shelf and to trust no one. Dale and Mo bicycle to the Colonel's house to get the packet. Mo takes a quick peek and sees that it contains old newspaper clippings. Before they have a chance to leave, a man enters through the front door. They figure it's Slate. He begins to rummage through the closets while they hide under Miss Lana's bed.
As they hear him leave, they hear a woman enter. They scramble toward the living room and run into Marla, the deputy, who points a gun at them. Unexpectedly, Marla isn't so friendly now. She puts away her gun, but interrogates the kids, wanting to know what they're up to. Mo throws a boot at Marla, and she falls, striking her head. The kids tie her up, flatten her tires and take off on Dale's bicycle.
En route to Dale's house, Mo is suddenly hit with the knowledge of where Slate is hiding Miss Lana — an abandoned house nearby. They bike to the abandoned house, but find it empty, though blood-stained. Then they head back to Dale's house where they play cards and wait out the storm.
All at once the door bursts open, and Dale's dad, drunk and angry, is in the room, even though Miss Rose has a restraining order against him. Mr. Macon physically assaults her, and Dale gets a rifle and aims it at him, telling him to get out or he'll kill him. Suddenly, the Colonel appears from a hallway, takes the rifle from Dale and iterates the threat. They tie up Mr. Macon and continue to wait out the storm. Mr. Macon tells them that Miss Lana is being held at Mr. Jesse's house. As they talk, they agree that Marla must have conned them all and was in league with Slate. The Colonel looks through the newspaper clippings in the packet that Miss Lana had saved for him. He knows he must be connected to the robbery, but he isn't sure how.
When the storm begins to abate, the kids and the Colonel, packing an empty pistol, take Miss Rose's car to Mr. Jesse's house. They sneak up to the house, and they split up, the Colonel going in one direction and the kids going in another. Dale and Mo observe Slate through a window as he pries up floorboards to reveal large spaces where things could be hidden but haven't been. Mo and Dale break into the house, kick Slate into the space under the floorboards and secure him by pulling a heavy oak table over the opening. When the Colonel returns, he uses a cord to tie up Slate, while Mo keeps the empty pistol trained on him. Next Starr appears at the door, and he has Miss Lana. She had escaped from Slate by hitting him with a lamp.
As the investigation winds down, Starr presents a newspaper clipping that upsets the Colonel because it shows that he was a defense lawyer at Slate's trial, and he hates lawyers. They find a metal box under the floor that contains the remainder of the bank robbery money. Slate and Marla are sent off to jail, and the town gets back to its routine, starting with a grand reopening of the café.