Johnson is one of some 5,000 plaintiffs across the USA and his victory is likely to lead to many more claims against Monsanto, which was recently bought by Geman chemical giant Bayer AG.
The lawsuit is the first to accuse the product of causing cancer, but observers say a Monsanto defeat likely opens the door to thousands of other claims against the company, which was recently acquired by Germany's Bayer.
In a landmark verdict, a jury in the U.S. has ruled that Monsanto's Roundup and other glyphosate-based weedkillers are linked to cancer, and directed the agro-giant to pay $289 million in damages to a school groundskeeper who developed the disease.
Dewayne Johnson reacts after hearing the verdict to his case against Monsanto at the Superior Court Of California in San Francisco, California, on August 10, 2018.
The Californian claimant, groundsman Dewayne Johnson, was diagnosed with non-Hodgkin's lymphoma in 2014.
"The jury found Monsanto acted with malice and oppression because they knew what they were doing was wrong and doing it with reckless disregard for human life", said Robert F. Kennedy Jr., one of Johnson's attorneys, according to the Associated Press.
The company, which has denied any link between the glyphosate, the active ingredient in Roundup, and cancer, vowed to appeal the verdict and "vigorously" defend its product.
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The manufacturer of the weedkiller, Monsanto, has insisted that British consumers are safe to continue using their Roundup products, which are widely sold at DIY stores and used by British farmers. "We are grateful to Mr. Johnson", he said, "for bravely facing down the "most evil corporation" in the world".
Environmentalists say the weedkiller is linked to cancer, although the claim is strongly denied by manufacturers and the European Union has approved the chemical for use.
Johnson's doctors testified he is unlikely to live past 2020.
The World Health Organisation classified the herbicide as "probably carcinogenic to humans" in 2015. In a review of the chemical previous year, it concluded glyphosate is likely not a carcinogen.
The EPA already had glyphosate on the list of hazardous substances for "chief-executive initiated" reassessment but she would ask EPA to consider adding Roundup as a "proprietary product" - which has other ingredients as well as glyphosate.
What became referred to as the "Monsanto Tribunal", in a purely advisory opinion, called for stronger laws protecting people and the environment from corporations, and a prosecutable crime of "ecocide".
Monsanto does not put a warning label on Roundup. Jurors awarded him $39 million for his losses and $250 million to punish the company after finding it liable for a design defect and failing to warn of Roundup's risks.
Monsanto was one of the companies that produced the defoliant "Agent Orange" - which has been linked to cancer and other diseases - for use by United States forces in Vietnam.