Plot

Vincent MacKenna (Bill Murray) is a Vietnam War veteran and retiree living in Sheepshead Bay, Brooklyn. Vincent is the son of Irish immigrants. He is a grumpy alcoholic who smokes and gambles regularly. His wife, Sandy, (Donna Mitchell) developed Alzheimer's disease years ago and can no longer recognize him, but he still does her laundry for her at the nursing home where she lives and visits her every week, posing as a doctor. Ana (Kimberly Quinn) is a nurse at the care facility where Sandy stays.

Otherwise, Vincent's only other close friends are a pregnant Russian prostitute named Daka (Naomi Watts) whom he has regular sex with, and his cat named Felix, as he owes many people money.

As Daka is heavily pregnant, she is not allowed to dance at the strip pole anymore, as she cannot get back up when she goes down in her routine.

Vincent has already reached the cash out limit on his reverse mortgage and the bank would not give him any more money against his property. Even his checking account is overdrawn by $112.14. Roger (Ray Iannicelli) is the local bartender who wants Vincent to ease up on the alcohol.

Despite leading a quiet and boring existence, Vincent has many acquaintances who like and respect him. One day, after Vincent's 30-year-old Chrysler Lebaron gets damaged by a tree branch resulting from his new neighbors moving in. Their moving truck backs into the driveway, but it was too tall and hits the branch of a tree that falls on Vincent's car.

The neighbors Maggie Bronstein (Melissa McCarthy) and her 12-year-old son Oliver, (Jaeden Lieberher) meet Vincent. Maggie is a radiology technician in the middle of a bitter divorce. Vincent demands payment for the damage to his car and fence (the damage to the fence he had actually done himself). Maggie offers to pay, but Vincent decides to sue the moving company for the damage to his car and asks Maggie to cover for the fence. Vincent habitually bets on horses at the racetrack and loses. Vincent owes money to the loan shark Zucko and says that he also has people to answer to. Vincent promises payments in a month but is given 2 weeks.

Maggie is a single mother fighting for custody after her husband had several affairs. Despite this, she is doing her best to provide for Oliver, who is ostracized and bullied at his Catholic school, but is nonetheless knowledgeable and friendly.

On his first day at his school, Oliver's phone and house keys are stolen from his gym locker. Brother Geraghty (Chris O'Dowd) is Oliver's teacher and an Irish priest. Coach Mitchell (Lenny Venito) is Oliver's P.E. teacher. Geraghty takes a class on what defines a saint. Oliver reports the theft and names a suspect from his class named Robert, due to which Robert gets detention.

Oliver asks Vincent if he can stay at his home until his mother comes home from work. Maggie is late and she pays Vincent for babysitting. Vincent negotiates a rate of $12 per hour to look over Oliver in Maggie's absence. Later he changes it to $11 per hour, if Maggie pays for the snacks.

Now that Vincent has money coming in, Vincent starts babysitting Oliver every day after school because Maggie often has to work late hours. Vincent's ideas of after-school activities involve visits to racetracks and bars, but eventually the mismatched pair begin to help each other mature.

Vincent sees Oliver being beaten up by Robert in a parking lot. He scares the bullies away and learns from Oliver that his father was a pacifist and never taught him to fight. Vincent teaches Oliver how to fight, and Oliver uses the technique to break the nose of his bully Robert (Dario Barosso), who later apologizes and gives back what he stole. Vincent and Oliver quickly become close friends and a lucky bet at the racetracks help Vincent to pay off some of his debts. Oliver learns all about horses, odds, trifectas and so on. Oliver suggests a trifecta that pays 800 to 1, and he bets $7, Vincent adds $3 from his side. Vincent deposits Oliver's sharing in a savings account that he opens in Oliver's name.

After staff in Sandy's nursing home remind him that he is behind on fees and tell him Sandy will be moved the next week if he does not pay what he owes in full, Vincent steals money from an account he set up for Oliver with their winnings from the track. He takes the money to the racetrack and gambles this money away hoping for a big win.

Vincent is confronted in his home by loan sharks Zucko and Antwan who attempt to take Sandy's jewelry. Vincent collapses while Zucko (Terrence Howard) and Antwan leave him on the floor. Oliver finds him and calls emergency services. Vincent is hospitalized, told he has had a stroke, and has to undergo physical therapy. Oliver, Maggie, and Daka help Vincent recover, but his language remains stunted.

Vincent becomes depressed after finding out that Sandy died while he was hospitalized. He is given a box containing her few belongings and her ashes. Meanwhile, Oliver's father blindsides Maggie in court with photographs of Vincent taking Oliver to inappropriate places. Now forced to share joint custody, a furious Maggie tells Vincent that he can no longer see Oliver.

For his "Saints Among Us" school project, Oliver asks around the neighborhood about Vincent's past. Later, he nominates Vincent at the school's assembly, publicly declaring him "St. Vincent of Sheepshead Bay" and presenting him with a medal. Oliver's rationale comes from his teacher's definition of sainthood as a person showing commitment, dedication and sacrifice. Vincent fits this in terms of his wife and he also saved two fellow soldiers during the Vietnam War. The school audience is impressed by Oliver's speech and applaud Vincent, who has been tricked into attending the event by Daka.

Some time later, Daka gives birth to a baby girl and she, along with Maggie, Oliver, and Robert, go to Vincent's house, where they eat together as a surrogate family.