The Supreme Court on Tuesday declined to hear a bid by Bayer AG to end thousands of lawsuits alleging its weedkiller Roundup causes cancer, potentially costing the German conglomerate billions of dollars in legal settlements.

Bayer has been mired in Roundup litigation since acquiring Monsanto, the product’s original owner, in 2018.

The German conglomerate, which maintains that Roundup is safe, has earmarked $16 billion to deal with litigation over the herbicide.

Last year, Bayer asked the high court to invalidate a $25 million jury verdict in favor of Ed Hardeman, who says decades of using Roundup on his Northern California property caused his non-Hodgkin lymphoma, a type of cancer.

The 2019 jury verdict in favor of Mr. Hardeman came in the first federal trial over whether Roundup’s active ingredient glyphosate causes cancer. The court’s denial bears not only on that case, but also on thousands of similar ones against the company.

“This has been a long, hard-fought journey to bring justice for Mr. Hardeman, and now thousands of other cancer victims can continue to hold Monsanto accountable for its decades of corporate malfeasance,” Hardeman’s trial lawyers, Jennifer Moore and Aimee Wagstaff, said in a statement.

Bayer has said those Roundup cases should be dismissed because the product was cleared by federal regulators.

The German conglomerate said Tuesday that the court’s decision to turn away the case undermines the ability of companies to rely on official actions taken by expert regulatory agencies. Bayer said there could be future Roundup cases that could lead to the high court revisiting the legal questions raised by the Hardeman case.

“Bayer continues to stand fully behind its Roundup products which are a valuable tool in efficient agricultural production around the world,” the company said.

Matthew Stubbs, a lawyer at the firm Duncan Stubbs who represents Roundup plaintiffs, said: “We’re grateful that SCOTUS has put an end to Bayer’s strategy of deny and delay.”

He added, “Today, SCOTUS has set a clear path for recovery in the courts, and we look forward to having jury trials throughout the country for decades to come.”

The U.S. Environmental Protection Agency has concluded that glyphosate isn’t a carcinogen, and Bayer has argued that Roundup’s warning label was based on these regulatory actions.

The verdict for Mr. Hardeman, which was upheld by an intermediate appeals court, “means that a company can be severely punished for marketing a product without a cancer warning when the near-universal scientific and regulatory consensus is that the product does not cause cancer, and the responsible federal agency has forbidden such a warning,” Bayer said last year.

The Supreme Court petition was one of the pillars of a five-point plan Bayer announced in May 2021 to deal with the Roundup litigation.

The plan also included beginning to remove glyphosate from Roundup sold to American residential consumers. Most of the Roundup cases involve such users.

Under Bayer’s plan, Roundup sold to commercial users will still include glyphosate. Commercial users account for the bulk of Roundup’s sales.

Ed Hardeman said decades of using Roundup on his Northern California property caused his non-Hodgkin lymphoma, a type of cancer.

Photo: noah berger/Agence France-Presse/Getty Images

Last month, Bayer’s stock fell 6.2% the day after the Biden administration recommended the Supreme Court decline to hear Bayer’s appeal. That move by the U.S. Justice Department appeared to diminish the chances of the court hearing the case.

A federal appeals court on Friday sided with environmental and food-safety advocacy groups in finding that the EPA has to re-examine whether glyphosate poses a health risk. In a 3-0 decision, the 9th U.S. Circuit Court of Appeals said the EPA didn’t adequately consider whether glyphosate causes cancer. “EPA’s ‘no cancer’ risk conclusion did not stand up to scrutiny,” said Amy van Saun, an attorney with the Center for Food Safety. A Bayer spokeswoman said the company believed the EPA would continue to conclude, as it had for years, that glyphosate-based herbicides aren’t carcinogenic.

Bayer has fared better in jury trials, securing four consecutive verdicts in its favor in Roundup jury trials. Most recently, on Friday, Bayer won a verdict that Roundup didn’t cause an Oregon man’s cancer.

Since the EPA concluded that glyphosate isn’t a carcinogen and can be used safely, Bayer argues that federal law pre-empts state law on labeling requirements.

In May, U.S. Solicitor General Elizabeth Prelogar filed a brief urging the court not to take up Bayer’s petition, maintaining that EPA labeling requirements don’t prevent states from adding their own labeling requirements. Some Wall Street analysts said chances were low that the court would take up the case after the solicitor general weighed in.

Agricultural lobbying groups and some lawmakers in Washington have warned of broader consequences on the development of future crop-protection chemicals if the Bayer case isn’t heard.

In May, 54 agriculture trade groups sent a letter to President Biden protesting the solicitor general’s stance on the Bayer case and urging the administration to withdraw the brief. They said they saw it as a concerning shift away from longstanding policy regarding the regulation and labeling of pesticide production that farmers and other users rely on. The agricultural groups said the solicitor general’s position essentially allows states such as California to misbrand a pesticide.

“At a crucial time when American farmers are striving to feed a world threatened by food shortages and insecurity, the likes of which we have not seen in decades, this reversal of policy greatly risks undermining the ability of U.S. agricultural producers to help meet global food needs,” wrote the trade groups, including the National Corn Growers Association, American Farm Bureau Federation and American Soybean Association.

About three-quarters of the claims against Roundup come from residential consumers rather than agriculture ones. Bayer executives argue that its agriculture users know the proper use of the product better than residential ones. They also say the Hardeman ruling, if allowed to stand, would jeopardize future pesticide production by discouraging companies from creating new products for fear of being mired in litigation.

Bayer says it has resolved around 107,000 of a total of 138,000 cases related to the herbicide.

—Patrick Thomas contributed to this article.