The verdict in the US state of Georgia marks the latest in a long-running series of court battles Monsanto has faced over its Roundup herbicide.
Germany-based Bayer, which acquired Monsanto in 2018, has continued to dispute claims that Roundup causes cancer.
The agrochemical giant says it will appeal the verdict, reached in a Georgia courtroom on Friday.
The penalties awarded include $US65 million ($A104 million) in compensatory damages and $US2 billion ($A3.2 billion) in punitive damages, law firms Arnold & Itkin LLP and Kline & Specter PC said in a statement.
That marks one of the largest legal settlements reached in a Roundup-related case to date.
Plaintiff John Barnes filed his lawsuit against Monsanto in 2021, seeking damages related to his non-Hodgkin's lymphoma.
Arnold & Itkin lawyer Kyle Findley, the lead trial lawyer on the case, said the verdict would help his client get the treatment he needs.
"It's been a long road for him ... and he was happy that the truth related to the product (has) been exposed," Findley told The Associated Press on Sunday.
He called the verdict an "important milestone" after "another example of Monsanto's refusal to accept responsibility for poisoning people with this toxic product".
But the company has been hit with more than 177,000 lawsuits involving the weedkiller and set aside $US16 billion ($A25 billion) to settle cases.
Monsanto said Friday's verdict "conflicts with the overwhelming weight of scientific evidence and the consensus of regulatory bodies and their scientific assessments worldwide".
The company said it continued "to stand fully behind the safety" of Roundup products.
For a variety of crops — including corn, soybeans and cotton — Roundup is designed to work with genetically modified seeds that resist the weedkiller's deadly effect. It allows farmers to produce more while conserving the soil by tilling it less.
Some studies associate Roundup's key ingredient, glyphosate, with cancer, although the US Environmental Protection Agency has said it is not likely to be carcinogenic to humans when used as directed.
Still, numerous lawsuits over the weedkiller allege glyphosate does cause non-Hodgkin lymphoma, arguing that Monsanto has failed to warn the public about serious risks for years.
Findley said that evidence relating to Barnes' case show "many years of cover-ups" and "backroom dealings".
He accused Monsanto of ignoring several scientific studies related to the toxicity of Roundup and said the company "tried to find ways to persuade and distract and deny the connection between this product and non-Hodgkin's lymphoma".
Friday's decision marks the fourth Roundup-related verdict that Findley's team has won.
The largest case was awarded in Philadelphia in January 2024, with damages totalling $US2.25 billion ($A3.58 billion).
Findley said his law firm had "many more clients who are similarly situated as Mr Barnes."
Monsanto said it had prevailed in 17 of the last 25 related trials, while some previous damage awards had been reduced.
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