Andrea "Andy" Sachs (Anne Hathaway) is an aspiring journalist fresh out of Northwestern University. Despite ridiculing the shallowness of the fashion industry, she lands the job "a million girls would kill for": junior personal assistant to Miranda Priestly (Meryl Streep), the icy editor-in-chief of Runway fashion magazine. Andy has to put up with Miranda's bizarre and humiliating treatment in hopes of getting a job as a reporter or writer somewhere else. At first, Andy fumbles with her job and fits in poorly with her catty coworkers, especially Miranda's senior assistant Emily Charlton (Emily Blunt).
During a dinner with her father who came to visit her in New York City, Miranda calls her: the airports in Florida where she is are all closed due to a hurricane but she needs to get home and orders Andy to get her home somehow. Andy tries every airline company there is, but none of them are flying out because of the weather. When Miranda does arrive back at the office she tells Andy she has disappointed her more than any other of her previous assistants.
Andy has a talk with Runway's art director Nigel (Stanley Tucci), who gives a whole new perspective of Miranda, her work and fashion in general. Andy decides to change and gradually learns her responsibilities and begins to dress more stylishly. Slowly but surely, Andy begins to sacrifice her personal life to her career. Miranda notices the change in Andy and gives her a new task: delivering "The Book" (a mock-up of the next edition's feature spreads) to her Upper East Side townhome. However, Andy is tricked by Miranda's daughters into going upstairs, where she inadvertently walks in on Miranda and her husband arguing. Mortified, she drops the book and leaves.
Miranda punishes Andy by giving her an impossible task: securing the unpublished manuscript for the next book in the Harry Potter series for her twin daughters to read on the train. Andy is just about to quit when Christian Thompson, a famous writer and acquaintance of Andy's informs her he has gotten it for her. Andy delivers the copies to a stunned Miranda and keeps her job, much to her boyfriend's disappointment.
When Emily falls ill, Miranda commands Andy to accompany the two of them to a charity benefit, where the two masquerade as partygoers while actually reminding her of important information about the people approaching her for a greeting. At the event, Andy saves Miranda from being embarrassed by Emily, who had forgotten one of the names; meets Jacqueline Follet, the editor-in-chief of French Runway and Miranda's rival; turns down an offer to meet a big publisher from Christian, but all the while misses her boyfriend's birthday party.
One evening, while returning The Book, Miranda informs her that she needs "the best team possible" for her Paris trip, which means stepping over Emily. Andy hesitates, as Emily has been boasting about going to Paris for months, but Miranda tells her that declining will send the message that she is not committed to her job or any future job at another publication. Andy has no choice but to accept. The next day Miranda then tells Andy to be the bearer of bad news to Emily who, meanwhile, is hurrying back to the office after purchasing scarves from Hermes of Paris for Miranda. Just as Andy is about to tell her, Emily crosses at a "no cross" point and is hit by a taxi. Andy has a rough day confronting Emily about Paris and then at her friend Lily's art gallery, where she accepts a kiss on the cheek from Christian. Lily catches this and berates Andy, to then confront her boyfriend about the fact that she is going to Paris. He realizes that they no longer have anything in common, and they break up.
In Paris, Andy attends the shows and even meets designer Garavani Valentino, being introduced as “the new Emily”. One night Andy comes into Miranda's suite only to find her in her bathrobe, undressed, and crying. While deciding on a seating chart, Miranda opens up saying that her husband is divorcing her, but that her biggest worry is for her daughters, who have lost yet another father figure. Later, Andy learns from Nigel that he has gotten a job as creative director at fashion designer James Holt's new company. Andy has dinner with Christian who figures out that she is single again. After a few glasses of wine she succumbs to Christian's charms and sleeps with him.
In his hotel room the next morning, while dressing, Andy finds out that Runway 's owner is planning to replace Miranda with Jacqueline Follet. Andy storms out to find Miranda and warn her. When Andy finally tells her, Miranda seems unfazed. At a luncheon in honor of James Holt, Miranda announces that Jacqueline will be the new creative director of James Holt's company much to the surprise of Andy and Nigel.
En route to another event, Miranda explains to a still-stunned Andy that she knew about the plan to get rid of her all along, but she found an alternative for Jacqueline and presented "the list" (a list of all the designers, stylists, company owners, and models that were "raised and nurtured" by Miranda and who have promised their loyalty to her whenever and should she ever leave Runway) to the owner of Runway, who realized that without those people, Runway would be doomed, was forced to reconsider. Miranda also says that she was pleased by Andy's display of loyalty and that she sees a great deal of herself in her. Andy says she could never do to anyone what Miranda did to Nigel. Miranda replies that she already did, stepping over Emily. Miranda tentatively comforts her, saying that those choices are necessary to live the life that she lives. At the event, Andy gets out of the car and simply walks away. When receiving a call from Miranda, she throws her phone into a fountain on the Place de la Concorde.
Back in New York, she meets her boyfriend for breakfast. He has accepted an offer to work as a sous-chef in a popular Boston restaurant. Andy is disappointed, but her hope is rejuvenated when he says they could work something out.
Andy goes to an interview for a newspaper job. The interviewer reveals that Miranda told him she was by far her biggest disappointment, but that if he did not hire her, he would be an idiot. Afterwards Andy calls Emily while walking past the Runway office and offers to send Emily all of the outfits Andy got while in Paris, Emily is a bit catty about this saying the clothes will "absolutely drown her" but accepts, after the call Andy then sees Miranda getting into her car across the street. They exchange looks and Andy smiles at her, but Miranda acts as if the two are strangers. Once in the car, Miranda gives a soft smile before angrily telling her driver, "Go!".
***
The novel begins with its main character, Andrea Sachs, stuck in midtown Manhattan traffic, trying to remember how to use a manual transmission. She is driving a Porsche roadster that belongs to her boss, Runway magazine editor Miranda Priestly. Sachs must deliver the roadster from the repair shop to Miranda's apartment in time for Miranda's family to go to the Hamptons for the weekend. While she is attempting to do this, Miranda calls Sachs on her cell phone and excoriates Sachs for not doing her job properly. Miranda also tells Sachs to pick up her pet French bulldog (Persian kitten in British edition) from the veterinarian's office. Trying to comply, Andrea ruins some of the expensive designer clothing she is wearing. She wishes Miranda would die. But if that did happen, she reminds herself, she would lose the pleasure of killing Miranda with her own hands.
Sachs had recently graduated Brown with a degree in English when she left her home in Avon, Connecticut for New York City. There she moved in with her longtime friend Lily, now doing graduate studies in Russian at Columbia. Sachs, a longtime reader of The New Yorker, blankets the magazine publishing industry with her résumé, hoping to land enough experience somewhere to eventually get her a job at the prestigious weekly. She gets a surprise interview at the Elias-Clark group and is hired on as Miranda's junior assistant. While she knows little of Miranda, she is told repeatedly that "a million girls would die for your job".
People at the magazine are afraid of finding themselves alone in an elevator with Miranda, or making critical remarks about her even to their close friends. Andrea dubs this attitude the Runway Paranoid Turnaround, as whenever one of her co-workers makes the slightest negative comment about Miranda, they immediately follow it up with a "turnaround" positive comment, due to their fear of their boss finding out about their attitude and firing them.
All the same, Andrea is told that if she manages to work for Miranda for a year, she can have her select pick of jobs within the magazine industry, so she valiantly struggles onward. Even in the present, the perks are generous — between Runway's notorious "closet" of designer clothes ostensibly "on loan" for photo shoots but rarely returned and often "borrowed" by the staff and the general obsequiousness she encounters as Miranda Priestly's personal assistant, she is able to acquire enough free designer clothing to fit in better with the rest of the fashionable Runway staff. Eventually, she develops an appreciation for it and stops incurring Miranda's displeasure. She gets a Bang and Olufsen phone for free when Miranda does not want it, and learns that Elias-Clark's policies regarding expense accounts are rather lax, to the benefit of herself and her friends.
She also goes to parties with celebrities. At one of them she meets Christian Collinsworth, a Yale graduate who has been identified as the hot (in more ways than one), up-and-coming writer of their generation. They become attracted to each other, complicating her relationship with Alex.
Sachs's job begins to affect her health; she starts to lose weight because she can't bring herself to eat. After years of being tall and fairly thin, Sachs finds herself the fat, lumpy dwarf of "Runway"'s office. Eventually, Sachs begins to rationalize her not eating by thinking thoughts like "Missing one meal won't hurt, and anyway, $2000 pants don't look so hot on a fat girl." She realizes that she has begun to adopt the Runway attitude for her own.
While working for Miranda, she receives a letter from a teenager, telling Miranda that she loves her magazine and spends all her money on trying to look like the models, but still hates herself because "my butt is huge" and "I'm too fat". The teenager begs Miranda to send her a dress to wear to her prom, but ends by telling her that, even if she throws the letter in the trash can, she will still love her. Andrea begins to doubt the true value of her job, as it is primarily encouraging the woman who makes teenagers all over America hate themselves as much as this one. However, she keeps going, thinking that it will all be worthwhile when she gets a job at The New Yorker.
The 14-hour days she puts in almost routinely leave her little free time to spend with Alex and Lily. Lily increasingly turns to alcohol and picking up dubious men to relieve the pressures of graduate school. Sachs's relationship with her family also suffers. Her parents complain that she doesn't visit her older sister, who is expecting her first child. Sachs stays absorbed in her own world as Lily's problems spiral out of control. Matters finally come to a head when Emily gets mononucleosis and Andrea must travel to Paris with Miranda. Andrea agrees, although this will mean canceling her trip for Alex's homecoming weekend.
In Paris, she has a surprise encounter with Christian. Later that night, Miranda finally lets down her guard a little bit and asks Andrea what she has learned, and where she would like to work afterwards. She promises to place phone calls to people she knows at The New Yorker on Andrea's behalf once her year is up, and tells her she can actually do some small written pieces for Runway.
But back at the hotel, Andrea gets urgent calls from Alex and her parents asking her to call them. She does so and learns that Lily is comatose in the hospital after driving drunk and wrecking a car.
Though Andrea is receiving pressure from her family and Alex to return home, she tells Miranda she will honor the commitment. Miranda is greatly pleased, and tells her that her future in magazine publishing is looking bright. At the Paris fashion show for Christian Dior, however, a livid Miranda phones her with yet another impossible demand. After she hangs up, Andrea stares at her phone, trying to think how to accommodate Miranda. Then, Andrea finally realizes that her family and friends are more important than her job, and realizes that she is becoming more and more like Miranda. On the spot, Andrea flips out her cell phone and tells her family that she is coming home. Miranda disapproves, but Andrea tells Miranda publicly "Fuck you, Miranda. Fuck you". She is fired on the spot, but returns home to reconnect with her friends and family. Her romantic relationship with Alex is beyond repair, but they remain friends. Lily recovers and fares well in court for her DUI charge, receiving only community service.
In the last chapter the reader learns that the fallout from her standup to Miranda made her a minor celebrity when the incident made 'Page Six'. Afraid she had been blacklisted for good from publishing, she stays in Connecticut for a while and works on short fiction. Seventeen buys one of her stories, and Andrea begins a friendly and professional relationship with Loretta, one of the editors of the teen magazine, who also happened to work for Runway prior to her tenure there. She returns to New York and gives herself a comfortable financial cushion by selling all the designer clothing she took to Paris with her to consignment shops. She saves a pair of Dolce and Gabbana denim jeans for herself, gave a quilted Chanel purse to her mother, and a Diane von Fürstenberg wrap dress to the teenager who wrote to Miranda.
At the novel's end, she is returning to the building to discuss a position at one of the company's magazines. She sees a girl whom she realizes is in fact, Miranda's new junior assistant, who is loaded with Miranda's coffee, shopping bags, newspapers, and her beaded clutch, and she remembers that that used to be her. The doorman tips Andrea a wink.
