In 1953, Katherine Ann Watson (Julia Roberts), a 30-year-old graduate student in the department of Art History at UCLA, takes a position teaching “History of Art” at Wellesley College, a conservative women’s private liberal arts college in Massachusetts because she wants to make a difference and influence the next generation of women. At her first class, Katherine discovers that the girls have already memorized the entire syllabus from the textbook so she instead uses the classes to introduce them to Modern Art and encourages spirited classroom discussions about topics such as what makes good art and what the Mona Lisa’s smile means. This brings her into conflict with the conservative College President (Marian Seldes) who warns Katherine to stick to the syllabus if she wants to keep her job. Katherine comes to know many of the students in her class well and seeks to inspire them to seek more than marriage to eligible young men. Joan Brandwyn (Julia Stiles) dreamt of being a lawyer and enrolled as pre-law so Katherine encourages her to apply to Yale Law School, where she is accepted. Joan, however, elopes with her fiancé Tommy (Topher Grace), and is very happy. She decides that what she wants most is to be a wife and mother after graduation and asks Katherine to respect her choice.
Betty Warren (Kirsten Dunst) is highly conservative like her mother, the head of the Alumnae Association. Betty doesn’t understand why Katherine is not married and is strident in insisting that there is a universal standard for good art. She writes two editorials for the college paper, one which exposes the nurse, Amanda Armstrong (Juliet Stevenson), for giving out contraception, which results in the nurse being fired, and one attacking Katherine for advocating that women should seek a career instead of just being wives and mothers as intended. Betty can’t wait to marry Spencer (Jordan Bridges) as their parents have arranged and expects to get the traditional exemptions from attending class because she is married, but Katherine insists she will be marked on merit.
Connie Baker (Ginnifer Goodwin) is dating Betty’s cousin, Charlie (Ebon Moss-Bachrach). Betty persuades her that he is only using her since it has been arranged by his parents for him to marry Deb, a girl more of his social standing. So, Connie ends the relationship. However, Charlie has already decided for himself that he is not going to marry Deb, so he and Connie get back together.
Giselle Levy (Maggie Gyllenhaal) has liberal views, and she supports Katherine because she sees her as having chosen what she wants in her life and because she herself has often felt out of place at the school being Jewish among the mostly WASP student body. Giselle brazenly has affairs with a professor and a married man.
Katherine confides to the girls that she was engaged when she was younger, but that she and her fiance were separated by the war. The relationship fizzled out, and she has since had several affairs. Katherine declines a proposal from her boyfriend (John Slattery) from California because she doesn’t love him enough. She begins seeing the Wellesley Italian professor, Bill Dunbar (Dominic West), who is charming and full of stories about Europe and his heroic actions in Italy during the war. He has also had affairs with many students (including Giselle), and Katherine makes him promise that it will never happen again. When Katherine learns that Bill spent the entire war at the Army Languages Center on Long Island, she decides to break up with him because he is not trustworthy. Dunbar responds that Katherine didn’t come to Wellesley to help the students, but to try to find herself.
Betty’s marriage fails miserably, as Spencer spends as much time as possible in New York on business. Giselle also catches Spencer having an affair. Betty’s mother tries to pressure Betty into remaining married to Spencer, at least for a while to avoid causing a scandal. Betty asks her mother if the Mona Lisa’s smile means she is happy. At graduation, Betty tells Katherine that she is divorcing Spencer. She adds that she is going to share a flat in Greenwich Village with Giselle, and that she is considering applying to Yale Law School.
Katherine’s course is highly popular, so the college invites her to return. But Betty’s mother and the president impose conditions on Katherine: she must follow the syllabus, submit lesson plans for approval, keep a strictly professional relationship among all faculty members, and not talk to the girls about anything other than classes. Katherine decides to leave, exploring Europe. In the ending scene, Betty dedicates her last editorial to her teacher Katherine Watson, claiming that Katherine is “an extraordinary woman who lived by example and compelled us all to see the world through new eyes.” As Katherine’s taxi speeds up, all her students follow on their bicycles and Betty is seen increasingly struggling to keep up with the taxi as a last effort to thank Katherine for changing her life.