Andy is an aspiring journalist fresh out of Northwestern University. Despite her ridicule for the shallowness of the fashion industry, she lands a job as junior personal assistant to Miranda Priestly, the editor-in-chief of Runway magazine, a job that "millions of girls would kill for". Andy plans to put up with Miranda's excessive demands and humiliating treatment for one year in the 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 gossipy, fashion-conscious co-workers. After she approaches art director Nigel to help her learn the ropes in the world of fashion, she begins to dress stylishly and starts showing effort for the position, accommodating all of Miranda's whims and fancies. Problems arise in her relationship with her chef boyfriend, Nate, who increasingly finds her spending all her time at her new boss's beck and call.
Miranda starts to notice Andy's changed appearance and commitment and begins to give her more responsibility and complicated tasks to handle. Slowly but surely, Andy becomes more glamorous and begins aligning herself, unwittingly at first, to the Runway philosophy. She gradually begins to outperform Emily (Miranda’s previous junior assistant who was promoted to 1st assistant) at her job.
Emily, meanwhile, is consumed with the thought of attending Paris Fashion Week as Miranda's assistant. At a charity benefit, she fails to provide information about a guest making his way to meet Miranda. Andy manages to save Miranda from embarrassment and is rewarded by being asked to replace Emily as Miranda's assistant at Fashion Week. Miranda tells Andy to inform Emily that she won't be going to Paris, but when Andy calls Emily, she is hit by a car and ends up in the hospital. She tells Emily the news, which infuriates her. When Andy tells Nate she is going to Paris, he is angered by her refusal to admit that she has become what she once ridiculed, and they break up.�
In Paris, Andy learns from Miranda herself about her impending divorce. Later that night, Nigel tells Andy that he has accepted a job as creative director with rising designer James Holt. Further, Andy spends the night with a young writer, Christian Thompson, who reveals to her that Miranda is set to be replaced by Jacqueline Follet as editor of Runway. Feeling bad for Miranda in her current situation, Andy attempts to warn her but does not manage to get through.
At a luncheon later that day, however, Miranda announces Jacqueline as the new creative director to Holt, leaving Andy and Nigel stunned. Later in the car, Miranda explains to Andy that she already knew of the plot to replace her and sacrificed Nigel instead to keep her own job. When Andy seems repulsed, Miranda points out that Andy did the same with Emily by stepping over her and agreeing to go to Paris. When they stop, Andy gets out and throws her cell phone into the fountain of the Place de la Concorde, leaving Miranda, Runway, and fashion behind.
Sometime later, Andy meets up with Nate and apologizes, though it is unclear if they eventually reconcile as Nate found a new job as a sous chef in Boston. The same day, Andy is interviewed and accepted to work at a major New York publication company. The editor recounts how he called Runway for a reference, and was told by Miranda herself that he would be an idiot not to hire Andy.