The justices in a 7-2 decision overturned a jury verdict in Missouri awarding $US1.25 million ($A1.81 million) to a man named John Durnell who said he was diagnosed with non-Hodgkin's lymphoma after years of exposure to glyphosate in Roundup.
The Supreme Court agreed with Bayer that a US law that governs pesticides precludes failure-to-warn claims that are brought under state law from moving forward in court.
Bayer acquired Roundup as part of its $US63 billion purchase of agrochemical company Monsanto in 2018.
More than 100,000 plaintiffs have filed cases in US state and federal courts alleging a cancer link, and the German drug making and crop science company had said that the lawsuits could threaten its ability to supply the herbicide to farmers.
The torrent of litigation already prompted Bayer to remove glyphosate from its consumer version of Roundup.
Bayer said before the Supreme Court ruled that a decision in its favour could largely end the Roundup litigation.
The Supreme Court heard arguments in the case in April.
"The US Supreme Court decision is good for science, farmers, and industries that depend on regulatory clarity for innovation. It should help significantly contain the Roundup litigation after nearly a decade of legal battles. The ruling should result in the dismissal of current warning-based claims and bar future failure-to-warn claims," company spokesman Tino Andresen said in a statement.
The company emphasised throughout the litigation that the US Environmental Protection Agency repeatedly found that glyphosate does not cause cancer and approved its product labels without a warning.
Facing billions of dollars in potential liability, Bayer announced in February a proposed $US7.25 billion settlement to resolve tens of thousands of current and future lawsuits.
The settlement would not affect claims that stem from pending appeals or that fall outside the deal, according to the company.
Those amount to nearly $US1 billion, it said.
Environmental activists and others criticised the court's ruling on Thursday.
"Once again, the Supreme Court has sided with big business over people and the environment. Today's ruling is a disaster for public health," said Tarah Heinzen, legal director at the advocacy group Food and Water Watch.
"The harm from this decision will perpetuate our cancer, infertility and general chronic disease epidemic for generations to come," said Kelly Ryerson, co-executive director of American Regeneration and a Make America Healthy Again activist who posts on social media under the moniker "The Glyphosate Girl".
The sprawling dispute centres on a US law called the Federal Insecticide, Fungicide and Rodenticide Act, or FIFRA, that governs the sale and labelling of pesticides and bars states from imposing differing or additional requirements.
The measure prohibits pesticides that are "misbranded" with labels that lack an adequate warning to protect health and the environment.
Bayer has argued that Durnell's claims are pre-empted by this law.
The EPA has repeatedly approved labels without such a cancer warning, demonstrating that these products are not misbranded, the company said, adding that labels cannot be substantially changed without the agency's approval.
Durnell's lawyers said that despite the EPA's registration of Roundup, the label may still be challenged as misbranded.
They also said Durnell's claims are not pre-empted because Missouri state law that requires products to adequately warn of dangers imposes the same requirements as FIFRA's prohibition on misbranding.
Durnell sued Monsanto in Missouri state court in 2019, claiming it failed to warn users of the dangers associated with Roundup and glyphosate.
He was diagnosed with a rare and often aggressive form of non-Hodgkin lymphoma, a cancer that starts in the white blood cells, and attributed the disease to his exposure to Roundup starting in 1996.
For about 20 years he was the "spray guy" for a neighbourhood association in St Louis, killing weeds at local parks without protective equipment, according to court papers.
A jury sided with Durnell in 2023, and in 2025 a state appeals court upheld that verdict.
