In 1962, aspiring author Barbara Novak arrives in New York to submit her book, Down with Love to Banner House publishing. It is about freeing women from love, enjoying sex without commitment, and replacing the need for a man with things such as chocolate. Barbara believes her rules will help boost women in the workplace and the world in general. When Banner House's male executives reject the book, Vikki Hiller, Barbara's editor, suggests Barbara meet with Catcher Block – a successful writer for Know magazine and a notorious ladies' man – to help promote the book. However, Catcher repeatedly avoids meeting Barbara until, fed up, she insults him. Catcher's boss and best friend, Peter MacMannus, and Vikki develop a mutual attraction, but neither is brave enough to express their feelings to the other. Peter feels overshadowed by Catcher's strong personality, and Vikki wants to see strength in her lover, even assuming Peter must be gay.
Barbara and Vikki persuade Judy Garland to sing "Down with Love" on The Ed Sullivan Show to promote the book. Sales skyrocket, as women around the world rebel against their men; Catcher now wants to meet Barbara but she rejects him. The breaking point comes as Barbara appears on a national TV show and discusses a chapter from her book – "The Worst Kind of Man" – and cites Catcher Block as the perfect example, causing the women he dates to reject him.
Catcher schemes to prove Barbara really wants love and marriage like every other women. He poses as Major Zip Martin, a polite and attentive astronaut. Barbara is immediately infatuated with a man who seems unaware of her celebrity, in contrast to the men who now avoid her since her book was published. As "Zip" takes her to fashionable New York locations, he maintains sexual tension by feigning naivete and a desire to remain chaste until he is "ready" for a physical relationship. His plan becomes complicated after he starts falling for her.
When Barbara encounters Catcher/Zip at a party, which nearly exposes his true identity, he decides to take everything to the next level. He tells Barbara Catcher Block wants to interview him for an exposé on the NASA space program and asks her to be there. At his apartment, he sets everything up to record her saying she loves him. Unfortunately, as they are about to have sex, one of his lovers, Gwendolyn, walks in. Not knowing who Barbara is, she exposes Catcher's identity, forcing him to confess to Barbara. Barbara then reveals she is actually Nancy Brown, one of Catcher's many former secretaries. She fell in love with him whilst working at Know. She had turned down a date with him, refusing to be another fling. She wanted to be different from the other women he knew, and make him fall in love with her. Catcher proclaims he wants to marry her, but Gwendolyn, having overheard Barbara Novak's name, thanks her for what she has done for womankind. Barbara realizes she does not want love or Catcher, as she has become a real "down with love" girl. Vikki and Peter's relationship also changes when she insults him for helping Catcher. Peter realizes he is indeed like any other man, and takes Vikki to Catcher's apartment to have passionate sex with her.
Days later, Catcher is completely depressed and has failed to win back Barbara. Even his exposé, which he wrote on how falling in love with her made him a better man, is ruined now Barbara has told her story in her own magazine, Now. Catcher goes to Now on the pretense of a job interview. He tells Barbara how much she has changed him and wishes there could be a middle ground for them, somewhere between her confident blonde persona and her original brunette self. After he leaves her office, she surprises him on the elevator, showing him a bright red hair style. she has found the middle ground and wants to be with him. They elope to Las Vegas, inspiring Vikki and Peter to also get married.
The end credits show Barbara and Catcher's marriage has resulted in a new book aimed at ending the battle of the sexes. The pair sing "Here's to Love".
Renée Zellweger as Barbara Novak
Ewan McGregor as Catcher Block
Sarah Paulson as Vikki Hiller
David Hyde Pierce as Peter MacMannus
Rachel Dratch as Gladys
Jack Plotnick as Maurice
Tony Randall as Theodore Banner
John Aylward as E.G.
Warren Munson as C.B.
Matt Ross as J.B.
Michael Ensign as J.R.
Timothy Omundson as R.J.
Jeri Ryan as Gwendolyn
Ivana Miličević as Yvette
Melissa George as Elkie
Dorie Barton as Sally
Matt Adler
Maggie Baird
John Cappelletti
Robert Clotworthy
Kat Cressida
Holly Dorff
Terri Douglas
Jessica Gee
John Gidcomb
Bridget Hoffman
Matthew Labyorteaux
Luisa Leschin
Hope Levy
Jessie S. Marion
Caitlin McKenna
Scott Menville
Tony Pope
Jill Remez
Clay Savage
Ron Snow
Steve Staley
Laura Summer
Mark Sussman