The story opens in Vevey, Switzerland, where twenty-seven-year-old American expat Winterbourne encounters a charming, irrepressible young compatriot named Daisy Miller. Daisy travels with her small, intractable brother Randolph and their ineffectual mother, accompanied by an immaculate courier named Eugenio. Winterbourne is simultaneously charmed and bewildered by Daisy's complete disregard for conventional social boundaries, as she chats freely with strangers and insists on touring the local castle alone with him, behavior that scandalizes Winterbourne's exclusive aunt, Mrs. Costello.
Months later, the scene shifts to Rome during the winter season. Winterbourne discovers that Daisy has plunged headfirst into Roman society, surrounding herself with a retinue of local admirers, most notably an opportunistic Italian named Giovanelli. American expatriates in Rome, including Winterbourne's acquaintance Mrs. Walker, turn their backs on Daisy, viewing her public promenades and nocturnal outings with Giovanelli as proof of a vulgar and reckless character. Winterbourne himself struggles to reconcile her apparent innocence with her seemingly defiant disregard for propriety.
Despite warnings from friends and the looming threat of the deadly Roman malaria, Daisy refuses to alter her habits. One night, Winterbourne stumbles upon Daisy and Giovanelli visiting the Colosseum by moonlight. Horrified by the obvious health danger, he rebukes them both before leaving her to her fate. Shortly thereafter, Daisy falls dangerously ill with the perniciosa.
During her final days, Daisy sends word to Winterbourne through her mother, insisting that she was never truly engaged to Giovanelli. She passes away and is buried in the Protestant cemetery in Rome. At the graveside, a grief-stricken Giovanelli insists to Winterbourne that Daisy was the most innocent young lady he had ever known. Winterbourne eventually returns to live in Geneva, left with the lingering realization that he misjudged a remarkably sincere spirit.
