New Year's Eve follows several interconnected stories of people experiencing various problems on New Year's Eve.
Vice-President of the Times Square Claire Morgan is making the final arrangements for the ball drop with the help of her friend, police officer Brendan. Meanwhile, after being nearly run over by a car and denied a vacation, Ahern Records secretary Ingrid Withers quits her job and offers deliveryman Paul Doyle tickets for the Ahern Records Masquerade Ball if he helps her complete her New Year's resolutions before midnight, and he accepts.
Paul's older sister Kim Doyle is having trouble with her teenage daughter Hailey, who wants to spend New Year's Eve with her friends and her boyfriend Seth Anderson in Times Square, though Kim wants to spend the New Year with her after her divorce. Paul's best friend, comic book illustrator Randy, hates New Year's Eve as his girlfriend left him on a date, gets stuck in an elevator with Elise, an aspiring singer providing back-up for musician Daniel Jensen at his Times Square show. Jensen is also preparing to perform at the Ahern Records ball while attempting to rekindle his relationship with his ex-fiancée, Laura.
At a nearby hospital, Claire's father Stan Harris, in the final stages of cancer who refuses chemotherapy and wishes only to see the ball drop one last time, is kept company by Nurses Aimee and Mindy after his doctor reveals he will not last much longer. In the same hospital, a young couple (Griffin and Tess Byrne) are about to have their first child, and compete with another couple, James and Grace Schwab, for a bonus offered to the family of the first child born in the New Year.
Elsewhere, Sam Ahern, Jr., a businessman and son of the late founder Sam Ahern, Sr. of Ahern Records, attempts to go to the Ahern Records Ball to deliver an important speech. After his car malfunctions in nearby Connecticut, all the while wondering if he should reunite with a mysterious woman he met and fell in love with on the previous New Year's Eve. Failing to find a mechanic or tow truck, Sam is able to get a ride from a cheerful family in an RV.
Later that evening, one of the LED panels on the Times Square Ball malfunctions, jamming the ball and forcing Claire to call "Kominsky", a disgruntled electrician whom the company had fired a few weeks prior. He repairs the ball before midnight, and, in gratitude, she leaves him in charge of the operation as she rushes to see the ball drop with her father, Stan. Meanwhile, Nurse Aimee has a video conference with her husband Chino, a soldier deployed in Afghanistan. Stan passes away just minutes after Claire snuck him up to the roof of the hospital to watch the ball drop, amid a chorus of "Auld Lang Syne", with Claire weeping beside him, holding his hand.
Paul helps Ingrid complete all the items on her list, and she gives him the tickets. They later say goodbye, but Paul decides to take her to the Ahern Records ball as his date. Meanwhile, Randy and Elise bond in the elevator as they share their lives and problems. Just as they are about to kiss, the elevator is repaired by the building superintendent and Elise rushes to Jensen's show. Randy notices she forgot her rubber bracelet and rushes to give it to her, still in pajamas. At Times Square, Jensen leaves midway through his show to return to the Ahern Ball to apologize to Laura, who takes him back and leaves with Sam's approval. With Jensen gone, Elise replaces him and attracts the attention of the crowd. She kisses Randy, and they start a romantic relationship.
Griffin and Tess have their baby and, although it is born first, they lie to allow James and Grace to have the $25,000 bonus after discovering they already have two other children to provide for. Meanwhile, after being forbidden from attending the celebration, Hailey runs away to Times Square, where she sees Seth being kissed by another girl, Lily, unaware that it was a kiss against his will. Heartbroken, she meets and is comforted by her mother. Kim finally realizes that she was too selfish for not allowing Hailey to spend the New Year with them. Seth finds them and apologizes, revealing Lily had stolen the kiss. Hailey forgives him and kisses him back. Her mother allows her to go to an after-party.
Kim then rushes to a restaurant to reunite with Sam, who had succeeded in delivering his speech. She is revealed to be the mysterious woman whom he met one year prior, and they finally share their names with each other. The film ends with Paul and Ingrid having fun at the Ahern Records ball party. As the credits roll, a series of bloopers and blunders are shared with the audience.
Jake T. Austin as Seth Anderson
James Belushi as Building Superintendent
Halle Berry as Nurse Aimee
Jessica Biel as Tess Byrne
Michael Bloomberg as himself
Jon Bon Jovi as Daniel Jensen
Abigail Breslin as Hailey Doyle
Ludacris as Lieutenant Brendan Nolan
Matthew Broderick as Mr. Buellerton
Robert De Niro as Stan Harris
Josh Duhamel as Sam Ahern, Jr.
Zac Efron as Paul Doyle
Héctor Elizondo as Lester Kominsky
Cary Elwes as Stan's Doctor
Carla Gugino as Dr. Morriset
Katherine Heigl as Laura
Cherry Jones as Mrs. Rose Ahern
Ashton Kutcher as Randy
John Lithgow as Jonathan Cox
Joey McIntyre as Rory
Katherine McNamara as Lily Bowman
Seth Meyers as Griffin Byrne
Lea Michele as Elise
Alyssa Milano as Nurse Mindy
Sarah Jessica Parker as Kim Doyle
Russell Peters as Sunil
Michelle Pfeiffer as Ingrid Withers
Sarah Paulson as Grace Schwab
Ryan Seacrest as himself
Til Schweiger as James Schwab
Hilary Swank as Claire Morgan
Sofía Vergara as Ava
Nat Wolff as Walter
Common as Chino
Sean O'Bryan as Pastor Edwin
Jack McGee as Grandpa Jed
Yeardley Smith as Maude
Penny Marshall as herself
Drena De Niro as Ahern Waitress
Christine Lakin as Waitress Alyssa
Shea Curry as Wendy
Amar'e Stoudemire as Party Dancer
Kathleen Marshall as Stage Manager Charlotte
Matthew Walker as Engineer Douglas
Peter Allen Vogt as Male Nurse
Fiona Choi as Balinese Woman
Mara Davi as Mika
Pat Battle as herself
New Year's Eve is the second in an unofficial trilogy of romantic comedy films directed by Garry Marshall, set on a one-day holiday and featuring an ensemble cast in a variety of stories, the other films being Valentine's Day (2010) and Mother's Day (2016).