In the winter of 1919, George (aged 12, portrayed by Bobby Anderson) and his friends (including Bert, Ernie Bishop, Marty Hatch, Sam Wainwright, and brother Harry) are sledding on a snow shovel down a slope onto a frozen river. When George's brother Harry sleds down, he breaks through the ice into the freezing water. George jumps in after him. His friends form a human chain and pull them to safety. George develops a cold which permanently affects the hearing in his left ear.
The following spring George goes to his job at Gower's Drug store, where he finds a telegram informing Gower that his son has died of influenza. Gower directs George to deliver medicine, and George realizes that in his distress Gower has inadvertently packaged poison. He seeks advice from his father, the President of the Bailey Bros. Building & Loan at his office, but is unable to as his father is meeting with banker Henry F. Potter. When he returns to the store, Gower angrily confronts him for failing to deliver the medicine until George points out the mistake. George promises that he will never tell anyone.
Nine years later, in the month of June, George (played by James Stewart) is preparing to leave town for an overseas trip. He drops by his brother Harry's graduation party at the high school, where he is re-introduced to his friend Marty Hatch's eighteen-year-old sister Mary. George is walking Mary home when a car pulls up and George is informed that his father has had a stroke.
Three months later, George is in a meeting with the board of directors of the Building & Loan to appoint a new successor to the late Peter Bailey. Potter argues that the Building & Loan should be dissolved. The directors tell George that the Building & Loan will only stay open if he agrees to remain and carry on his father's work. George foregoes a trip to Europe and his plans for college, giving the funds saved toward tuition to his younger brother.
Four years later, George and Uncle Billy are waiting at the Bedford Falls railroad station for Harry to come home from college, when Harry arrives with his new wife, Ruth. Her father has offered Harry a job, which means he will not be taking George's place at the Building & Loan. George is stuck in Bedford Falls. While the family is celebrating Harry's return, Ma Bailey mentions to George that Mary Hatch is back from college and he should pay her a visit. He eventually goes to Mary’s home to visit her, only to find that she is being courted by his friend, the now wealthy but absent, Sam Wainwright.
A few months later, George and Mary are married. Their plans for a honeymoon in New York City and Bermuda are interrupted by a run on the banks which also affects the Building & Loan. Potter's bank calls their loan, and panicked depositors want their money, threatening to take their business to the bank. As a stockholder, Potter threatens to shut the Building & Loan if they are forced to close early. Mary and George use the money saved for their honeymoon to keep the Building & Loan solvent.
Two years later, thanks to the Building & Loan, the Martini family move out of 'Potter's Field' to the new 'Bailey Park', a residential development created by George that proves successful enough to seriously threaten Mr. Potter's rental interests. Potter offers George a job. Although this would bring a significant increase in salary George declines. George returns home to learn that Mary is pregnant. Their first child is a son they call Pete. Their second child is a daughter, Janie.1939–45
During the war years, George and Mary had another two children, a girl, Zuzu, born in 1940, and a son, Tommy, born in 1941. Due to George's deaf ear he was given a 4-F draft classification and had to stay in Bedford Falls. His friend Bert the Cop went to Africa to fight and got wounded, but was awarded the Silver Star. Ernie was a member of the airborne and parachuted in on D-Day, and Marty helped capture the Bridge at Remagen. Harry fought as a naval flyer and shot down fifteen planes, two of which were attacking a troop transport. For his bravery he was awarded the Medal of Honor by the President of the United States. Sam made a lot of money making plastic hoods for planes. While all this happened, George served as an Air Raid Warden. Despite having to look after four children, Mary still had time to run the United Service Organizations in the town. Mr Potter became head of the draft board.Christmas Eve 1945
On Christmas Eve morning, Uncle Billy is on his way to the bank to deposit $8,000 of the Building & Loan's cash funds. Holding a newspaper which has Harry on the front page he greets Potter saying, "Well, good morning, Mr. Potter. What's the news?" Billy grabs Mr. Potter's newspaper and says, "Well, well, well, Harry Bailey wins Congressional Medal. That couldn't be one of the Bailey boys? You just can't keep those Baileys down, now, can you, Mr. Potter?" Potter angrily snatches the paper, but Billy inattentively allows the money to be snatched with it. Potter opens the paper, notices the money and keeps it, knowing that displacement of bank money would result in bankruptcy for the Building & Loan and criminal charges for George. Billy goes back to the Building & Loan and tells George the news. George is extremely worried, especially with the bank examiner just outside the room. George and Billy go through the town taking every step Billy took in the morning and it goes to a dead end. George later goes home and Mary knows straight away something is wrong with him. To add to his anger, he finds out his youngest daughter Zuzu has come home with a cold, George blames it on her teacher and when she rings he abuses her on the phone, and also her husband. He then gets frustrated with his family and ends up smashing up the models of buildings and bridges he had made.
A desperate George appeals to Potter for a loan. Potter sarcastically turns George down, and then swears out a warrant for his arrest for bank fraud. George, now completely depressed, gets drunk at the bar owned by his friend, Martini, where he silently prays for help. He also gets a full punch to the face from Zuzu's teacher's husband, who is drinking there. Again George runs out, and drives his car into a tree. He comes to a bridge intending to commit suicide, feeling he is "worth more dead than alive" because of a life insurance policy. Before he can leap, another man jumps in first and pretends to be drowning. After George rescues him, the man reveals himself to be George's guardian angel, Clarence Odbody.
George does not believe him and he bitterly wishes he had never been born. Inspired by this comment, Clarence shows George what the town would have been like without him, with the snow outside stopping as the change is made. In this alternate scenario Bedford Falls is instead named Pottersville, and is home to sleazy nightclubs, pawn shops, and amoral people. Bailey Park was never built, and remains an old cemetery. Mr. Gower was sent to prison for poisoning the child and is despised and homeless. Martini does not own the bar. George's friend Violet Bick is a taxi-dancer who gets arrested. Ernie is helplessly poor, with his family having forsaken him. Uncle Billy has been in an insane asylum for many years since he lost his brother and the family business. Harry is dead as a result of George not being there to save him from drowning, and the servicemen he would have saved also died. Ma Bailey is a bitter widow, and Mary a shy, single spinster librarian.
George runs back to the bridge and begs to be allowed to live again. His prayer is answered, shown as the snow restarts, and he runs home joyously, where the authorities are waiting to arrest him. Mary, Uncle Billy, and a flood of townspeople arrive with more than enough donations to save George and the Building & Loan. George's friend Sam Wainwright sends him a $25,000 line of credit by telegram. Harry also arrives to support his brother, and toasts George as "The richest man in town". In the pile of donated funds, George finds a copy of The Adventures of Tom Sawyer inscribed, "Dear George: Remember no man is a failure who has friends. P.S. Thanks for the wings! Love, Clarence." A bell on the Christmas tree rings, and his daughter Zuzu says, "Teacher says every time a bell rings, an angel gets his wings!" George agrees and looks up to heaven and says, "Attaboy, Clarence." George realizes that he truly has a wonderful life.
Citing generosity as Bailey's most admirable trait, Time magazine lists George Bailey among their top ten movie dads.