The jury deliberated for three days before concluding that the firm had failed to warn its clients about cancer risks associated with the product's main ingredient, glyphosate, USA Today reported.
Judge Suzanne Ramos Bolanos said in court Monsanto, which was acquired in June by German pharma giant Bayer, "acted with malice, oppression or fraud and should be punished for its conduct."
The 46-year-old plaintiff, DeWayne Johnson, came in contact with the substance for years as a school groundkeeper, using up hundreds of gallons at a time, his lawyer reportedly said.
He was diagnosed with non-Hodgkin's lymphoma in 2014, a type of cancer that affects white blood cells. A year later, the World Health Organization concluded that glyphosate was probably carcinogenic.
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The landmark ruling opens the door to thousands of similar cases from US plaintiffs. Monsanto Vice President Scott Partridge said the company would appeal the verdict.