In 1974, Karen Silkwood (Meryl Streep) along with her colleagues Drew Stephens (Kurt Russell) and Dolly Pelliker (Cher), report for duty at the Kerr-McGee Cimarron nuclear facility located near Cimarron City, Oklahoma. Karen is employed in Dry Processing, where her role involves converting plutonium and uranium oxide into nuclear fuel pellets. During an orientation for new trainees at the facility, the plant manager downplays the dangers of radiation exposure, likening it to a sunburn—implying it poses negligible harm if precautions are taken.
As lunch is announced, Karen, eager to leave, hastily removes her protective gear but is admonished by her coworkers for not being vigilant. Before stepping out, she passes her bare hands over a radiation detector.
In the lunchroom, she overhears talk about a truck that has been contaminated due to a leak. Karen learns that Drew has to stay late, leaving her frustrated as she searches for foreman Mace Hurley (Bruce McGill) to request time off to see her children. She encounters Winston (Craig T. Nelson), a newcomer in X-Ray Metallography; when Drew teasingly wonders if she likes him, she bluntly replies, “As a matter of fact, he's the type I hate.” Unfortunately, when she confronts Mace, he informs her that the plant operates around the clock, denying her weekend leave.
Trying to shuffle her weekend shifts, Karen is interrupted by an alarm that they suspect is a drill. However, she and her colleagues note that despite frequent tests, actual evacuations never occur, presumably to avoid disrupting production. The ever-reluctant Gilda Schultz (E. Katherine Kerr) eventually agrees to cover for her. On that fateful Saturday, the trio—Karen, Drew, and Dolly—travel to Texas to take her children to the beach. However, Karen’s ex-husband, Pete Dawson (Ray Baker), disrupts their plans with his own arrangements, though he allows a brief visit with the kids.
Later, during her return to work on Monday, Karen's friend Joe (Will Patton) mentions his involvement in disposing of the contaminated truck, raising alarm bells for her. In the dressing room, she discovers that Gilda failed to cover her shifts, leaving her concerned about being held responsible for a contamination incident right after her departure. As Karen dons a full hazmat suit upon entering her work area, she finds her coworkers in similar attire, following a sudden scrub-down by a cleanup crew. Disturbingly, Quincy Bissell (Henderson Forsythe), the union shop steward, enlightens her on the harsh reality that someone must take the blame to safeguard the company’s interests.
Their workspace becomes increasingly fraught when Thelma Rice (Sudie Bond), an older colleague and friend, is involved in a radiation accident. After undergoing decontamination, Thelma receives reassurances from the doctor about her health, but Karen fears the worst for her friend.
As Karen becomes more aware of the hazardous conditions, she begins to realize that the information claiming "acceptable levels" of radiation exposure may be misleading. Moving to the Metallography department means Karen must now wait an additional three months for overtime eligibility. Here, she unearths troubling practices when Winston is caught manipulating photographic records to conceal the flaws in the fuel rods.
During a union meeting, Quincy shares that they are positioned to organize a desertification vote, prompting Karen to step forward as a volunteer. Despite Drew's skepticism about her negotiation prowess, she resolutely aims to stand her ground against Mace Hurley. Meanwhile, Dolly’s romantic entanglement with beautician Angela (Diana Scarwid) escalates tensions within their shared space.
With increasing urgency, Karen, now more entrenched in her fight for worker rights, discovers alarming practices at the plant and decides to seek higher representation. A meeting in Washington, D.C. reveals the national union's emphasis on safety, but Karen must present solid evidence regarding her claims of misconduct and negligence, particularly the doctored photographs.
Back home, the repercussions of her activism take a toll on her personal life, leading to estrangement from Drew, who abruptly quits his job. In a twist of events, Karen feels isolated not only from her colleagues but also from the management.
Amidst persistent deterioration in her health, an accident occurs when she hits a deer, leading to a further series of ominous events that unravel her world—culminating in a car crash that leaves her lifeless. The haunting inscription on her tombstone reads: "Karen Gay Silkwood; February 19, 1946 - November 13, 1974; Rest in Peace."
The story closes with a powerful reminder that the exact details surrounding her untimely death remain shrouded in mystery, underscored by the chilling context that no incriminating documents were found, and an autopsy revealed a lethal mix of drugs in her system. Law enforcement deemed her demise an unfortunate single-car accident, while the plant itself eventually ceased operations a year later.
