In 1957, the legendary singer Billie Holiday sits down for an interview with radio journalist Reginald Lord Devine. During their discussion, Devine probes her about the challenges she faces as a "colored woman" and the backlash surrounding her powerful song "Strange Fruit." Billie passionately explains that the song's lyrics highlight crucial human rights issues, which are often neglected by those in power.
Flashback to 1947, where Billie's husband James Monroe and her manager Joe Glaser urge her to remove "Strange Fruit" from her performance repertoire due to potential legal complications. Despite their concerns, Billie's saxophonist and steadfast ally, Lester Young, stands by her, encouraging her to keep the song in her set.
As the 1940s unfold, Harry J. Anslinger, the head of the Federal Bureau of Narcotics, marks Billie as a major target, perceiving her as a political threat because of her music's provocative themes. Unable to charge her with merely singing, the authorities pivot to alleged drug offenses. After one of her performances, undercover agent Jimmy Fletcher, posing as a soldier, witnesses Billie using drugs. The ensuing investigation leads to her arrest alongside her partner Joe Guy. Betrayed by the testimony of a bribed witness, Billie receives a harsh one-year prison sentence.
Assigned to gain Billie's trust, Jimmy visits her in prison, initially aiming to extract incriminating evidence. However, he becomes sympathetic to her plight and advises her to stay vigilant, knowing the government is intent on destroying her legacy.
Upon her release, Billie returns to the stage at Carnegie Hall but is saddened when she must turn down a fan's request to hear "Strange Fruit." She subsequently meets promoter John Levy, who offers to help her navigate the treacherous waters of her career. Sadly, Levy's betrayal comes full circle when he plants drugs on her, resulting in another arrest just as Anslinger's agents close in. In a dramatic court scene, Jimmy reveals that Billie may have been set up, leading to her freedom once more.
In 1949, after a successful string of performances, Jimmy finally comes clean about his true allegiance to the Bureau. Desperate to earn Billie's trust again, he shares his struggles with addiction, and their relationship deepens as they fall in love. However, after a bus breakdown prompts an emotional farewell, Billie believes that she is not the right partner for Jimmy, prompting him to leave.
Later, Billie marries Louis McKay, but her heart ultimately belongs to Jimmy. As 1959 rolls around, an older Billie lies dying in a hospital bed after years of battling alcoholism. In a final confrontation, Anslinger pays her a visit with one last deal—clearing her record in exchange for names of fellow drug users. Billie, unfazed, delivers a powerful retort, stating that his grandchildren will one day be singing "Strange Fruit."
