Andrea Sachs, a recent graduate of Brown University with a degree in English, moves to New York City with her best friend, Lily, a graduate student at Columbia. Andrea hopes to find a career in publishing and blankets the city with her résumé. She believes she'll be closer to her dream of working for The New Yorker if she can get a job in the magazine industry. She gets a surprise interview at the Elias-Clark Group and is hired as junior assistant for Miranda Priestly, editor-in-chief of the fashion magazine Runway . Although she knows little of the fashion world, everyone tells her that "a million girls would die for [her] job". If she manages to work for Miranda for a year, people tell her, she can have her choice of jobs within the magazine industry.
At a celebrity party, Andrea meets Christian Collinsworth, a charismatic Yale graduate who is considered one of the hot, new up-and-coming writers of their generation. They are attracted to each other, which complicates her relationship with her boyfriend, Alex.
Andrea's relationships become entangled because of her new job. Lily increasingly turns to alcohol and picks up dubious men to relieve the pressure of graduate school. Alex, struggling with his own demanding job as an inner-city schoolteacher, grows frustrated with Andrea's long hours and constant stress. Andrea's relationship with her family also suffers. Matters finally come to a head when her co-worker, Emily, gets mononucleosis and Andrea must travel to Paris with Miranda in her stead. In Paris, she has a surprise encounter with Christian. Later that night, Miranda finally lets down her guard and asks Andrea what she has learned, and where she wants 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 suggests she take on some small writing assignments at Runway .
Back at the hotel, Andrea gets urgent calls from Alex and her parents asking her to call them. She does and learns that Lily is comatose after driving drunk and wrecking a car. Though her family and Alex pressure her to return home, she tells Miranda she will honor her commitment to Runway . Miranda is pleased, and says her future in magazine publishing is bright, but phones with another impossible demand at Christian Dior's Paris fashion show. Andrea decides that her family and friends are more important than her job, and realizes to her horror that she is becoming more and more like Miranda. She refuses to comply with Miranda's latest outrageous request, and when Miranda scolds her publicly, Andrea replies, "Fuck you, Miranda. Fuck you ." She is fired on the spot, and returns home to reconnect with friends and family. Her romantic relationship with Alex is beyond repair, but they remain friends. Lily recovers and is lucky to receive only community service for her DUI charge.
In the last chapter Andrea learns her dispute with Miranda made her a minor celebrity when the incident made " Page Six ". Afraid she has been blacklisted from publishing for good, she moves back with her parents. She works on short fiction and finances her unemployment with profits made from reselling the designer clothing she was provided for her Paris trip. Seventeen buys one of her stories. At the novel's end, she returns to the Elias-Clark building to discuss a position at one of the company's other magazines and sees Miranda's new junior assistant, who looks as harried and put-upon as she once did.