In Edwardian London, 1910, Cockney one-man band Bert is entertaining a crowd when he senses a change in the wind. Afterwards, he directly addresses the audience and gives them a tour of Cherry Tree Lane, stopping outside the home of the Banks'. George Banks returns home from his job at the bank to learn from his wife Winifred that their hired nanny, Katie Nanna, has left their service after his children, Jane and Michael, ran away again. They are returned shortly after by the local constable, who reveals that the children were dragged away by their kite. The children ask their father to help build a better kite, but he dismisses them. Taking it upon himself to hire a nanny, George advertises for a stern, no-nonsense nanny. Jane and Michael present their own advertisement for a kinder, sweeter nanny, but George rips up the letter and throws the scraps in the fireplace, which magically float up and out into the air.
The film follows the exploits of Alexander Cooper (Ed Oxenbould), an ordinary 11-year-old boy, and his "terrible, horrible, no good, very bad day." He is left out by his family; his older brother, Anthony (Dylan Minnette), his older sister, Emily (Kerris Dorsey), his mother, Kelly (Jennifer Garner), his father, Ben (Steve Carell), and his baby brother, Trevor (Elise/Zoey Vargas), living in the Los Angeles metropolitan area of California.
Sheryl Hoover (Toni Collette) is an overworked mother of two living in Albuquerque, New Mexico. Her brother, Frank (Steve Carell), is a scholar of French author Proust and a homosexual, temporarily living at home with the family after having attempted suicide. Sheryl's husband Richard (Greg Kinnear) is a Type A personality striving to build a career as a motivational speaker and life coach. Dwayne (Paul Dano), Sheryl's son from a previous marriage, is a Nietzsche-reading teenager who has taken a vow of silence until he can accomplish his dream of becoming a test pilot. Richard's foulmouthed father, Edwin (Alan Arkin), recently evicted from a retirement home for snorting heroin, lives with the family; he is close to his seven-year-old granddaughter Olive (Abigail Breslin).
London journalist Martin Sixsmith has lost his job as a government adviser. He is approached at a party by the daughter of Philomena Lee. She suggests that he write a story about her mother, who was forced to give up her toddler son Anthony nearly fifty years ago. Though Sixsmith is initially uninterested in writing a human interest story, he meets Philomena and decides to investigate her case.
Rebecca (Olivia DeJonge) and Tyler (Ed Oxenbould) prepare for a week-long stay with their grandparents, John (Peter McRobbie) and Doris (Deanna Dunagan), while their mother, Paula (Kathryn Hahn), goes on a cruise with her new boyfriend. The two kids, who have never met their grandparents, intend to film a documentary about their visit. Paula has not seen her parents in 15 years, after she eloped with her high-school teacher, Robert, who has since left her. She tells Rebecca little about the disagreement she had with her parents, suggesting that Rebecca ask them for more details.
Major Bennett "Ben" Marco (Denzel Washington) is a war veteran who begins to doubt what is commonly known about his famous U.S. Army unit. During the Gulf War, Sergeant First Class Raymond Shaw (Liev Schreiber) supposedly rescued all but two members in his unit, of which Marco was the commanding officer. Shaw became a war hero and was awarded the Medal of Honor, launching his political career.
On October 30, Devil's Night in Detroit, Sergeant Albrecht is at the scene of a crime where Shelly Webster has been beaten and raped, and her fiancé Eric Draven then died on the street outside, having been stabbed, shot, and thrown out of the window. The couple were to be married the following day, on Halloween. As he leaves for the hospital with Shelly, Albrecht meets a young girl, Sarah, who says that she is their friend, and that they take care of her. Albrecht tells her that Shelly is dying.
Micky Ward (Mark Wahlberg) is an American welterweight boxer from Lowell, Massachusetts. Managed by his mother, Alice Ward (Melissa Leo), and trained by his older half-brother, Dicky Eklund (Christian Bale), Micky has not had a particularly successful career: He's become a "stepping stone" for other boxers to defeat on their way up. Complicating matters, Dicky, a former boxer whose peak of success was going the distance with Sugar Ray Leonard in 1978 (before Leonard became a world champion), has fallen apart since then, becoming addicted to crack cocaine. He is now being filmed for an HBO documentary he believes to be about his "comeback".
Set in the fictional town of Thayer, Massachusetts, the story focuses on Meredith Morton (Sarah Jessica Parker), a successful Manhattan executive whose uptight, conservative demeanor is a sharp contrast to that of her boyfriend Everett Stone (Dermot Mulroney) and his liberal and rambunctious family.
The seemingly random murder of their adoptive mother, Evelyn Mercer (Fionnula Flanagan), at a Highland Park, Michigan convenience store, brings four brothers back home to Detroit, Michigan to find out what happened. Originally under the impression the crime was a simple robbery-gone-wrong, the brothers soon discover that the robbery was merely a cover for what was, in fact, a hit put out on Evelyn. After this revelation, Bobby (Mark Wahlberg), Angel (Tyrese Gibson), Jeremiah (André Benjamin) and Jack Mercer (Garrett Hedlund) track down the hired guns who killed Evelyn. Refusing to say anything, they are unceremoniously executed by Bobby and Angel.
In 1986, Nick Parker (Dennis Quaid) and Elizabeth James (Natasha Richardson) meet and get married during an ocean cruise on the RMS Queen Elizabeth II. After the birth of their twin daughters, Annie and Hallie (Lindsay Lohan), Nick and Elizabeth divorce and lose contact, each parent raising one of the twins without telling her about her sister. Nick raises Hallie in Napa Valley and becomes a wealthy wine grower, while Elizabeth raises Annie in London and becomes a famous and wealthy wedding gown designer.
In the year 1990, Iqbal Haroon Khan (Jackie Shroff) runs The Great Indian Circus in Chicago, which has fallen on bad times. Anderson's (Andrew Bicknell) bank — Western Bank of Chicago —, which has lent money to Iqbal Khan, decides to close down the circus when Khan is unable to repay the loan. Young Sahir (Siddharth Nigam), the little son of Iqbal Khan, pleads with Anderson not to shut down his father's circus, as he and his father would soon be able to turn the corner. But Iqbal Khan's presentation before the bankers and Sahir's pleas don't help. Iqbal Khan commits suicide in front of the heartless Anderson, leaving Sahir devastated.
George Banks (Steve Martin) is the owner of an athletic shoe company in San Marino, California, whose 22-year-old daughter, Annie (Kimberly Williams), returns from Europe, telling them she is engaged to Bryan MacKenzie (George Newbern), a man from an upper-class family from Bel-Air, despite them only having known each other for three months. The sudden shock turns the warm reunion into a heated argument between George and Annie, but they quickly reconcile in time for Bryan to arrive and meet them. Despite Bryan's good financial status and likeable demeanour, George takes an immediate dislike to him while his wife, Nina (Diane Keaton), accepts him as a potential son-in-law.
Homer Wells, an orphan, grows up in a Maine orphanage directed by kindly, avuncular Dr. Wilbur Larch. Homer is returned twice by foster parents; his first foster parents thought he was too quiet and the second parents beat him. Dr. Larch is addicted to ether and is also secretly an abortionist. Conditions at the orphanage are very spartan, but the children are treated with love and respect, and they are like an extended family. Each night before they go to sleep, Dr. Larch says, "Goodnight you princes of Maine, you kings of New England!" as both encouragement and a kind of blessing.
Bob Munro (Robin Williams), a successful California beverage company executive, is struggling with a dysfunctional family, with his materialistic wife Jamie (Cheryl Hines), his sharp-tongued teenage daughter Cassie (JoJo), and his son Carl (Josh Hutcherson), who is an adolescent weightlifter and likes Hip hop. At a company picnic, Bob is embarrassed in front of his self-absorbed boss Todd (Will Arnett) by Cassie's militant friend Gretchen, who hurls a tub of disgusting slime over Todd. Looking forward to a big family vacation in Hawaii, their trip is cancelled when Todd, out of spite, tells Bob that he has to attend a meeting with the Alpine Soda company in Boulder, Colorado instead, or else he will be fired. Concealing the real reason for going there, he rents a garish RV from the dodgy dealer Irv (Barry Sonnenfeld) and tells his family they are traveling to the Rockies.