A San Francisco jury found the firm, which is owned by Bayer- German multinational pharmaceutical and life sciences company, had been "negligent by not using reasonable care" to warn of the risks of its product, ordering it to pay Edwin Hardeman US$75 million in punitive damages, US$5.6 million in compensation and US$200,000 for medical expenses.
The jury also found that Roundup's design was defective and that the product lacked sufficient warnings of potential risk.
The same jury had previously found that a quarter century exposure to Roundup, whose principal ingredient is controversial chemical glyphosate, was a "substantial factor" in giving the 70-year-old Hardeman non-Hodgkin's lymphoma.
The verdict marks a major setback for Bayer, which purchased Monsanto last year for US$63 billion and has seen its shares plunge because of the litigation.
Hardeman's attorneys, who cheered and hugged their client as the verdict was announced, said they were pleased the jury had unanimously ruled in his favor and that Monsanto was being held accountable.
"It is clear from Monsanto's actions that it does not care whether Roundup causes cancer, focusing instead on manipulating public opinion and undermining anyone who raises genuine and legitimate concerns about Roundup," attorneys Aimee Wagstaff and Jennifer Moore said in a statement.
"It speaks volumes that not one Monsanto employee, past or present, came live to trial to defend Roundup's safety or Monsanto's actions."
The case is one of more than 11,200 similar cases in the U.S. alone involving Roundup.
Last year, Monsanto lost a case to a California school groundskeeper suffering from terminal non-Hodgkin's lymphoma, who had sued the company over the glyphosate weedkillers Roundup and Ranger Pro.
Monsanto was initially ordered to pay US$289 million to Dewayne Johnson, before the damages were reduced to US$78.5 million.
Bayer has also filed an appeal in that case.
Monsanto has consistently denied that the weedkiller causes cancer and challenged findings by the International Agency for Research on Cancer, an agency of the World Health Organization (WHO), which classified glyphosate as a "probable carcinogen" in 2015.
But other major agencies like the European Food Safety Authority (EFSA), the European Chemicals Agency (ECHA) or the U.S. Environmental Protection Agency (EPA) have not followed suit.
Carl Tobias, a law professor at the University of Richmond, told AFP that Hardeman's case was "important as a bellwether, which means it helps predict how future cases will be decide."
Tobias said the verdict "bodes well" for plaintiffs in the thousands of other cases filed against Monsanto, and was "likely to encourage plaintiffs and their counsel to be more vigorous in pursuing their cases and will lead more potential plaintiffs to file suit."
The Environmental Working Group, a non-profit, cheered Wednesday's verdict.
"Clearly, the testimony that informed the jury's decision was Bayer-Monsanto hiding Roundup's carcinogenic properties, manipulating the science and cozying-up with EPA so it would not have to warn consumers of its dangerous product," said the group's president Ken Cook.
"Bayer-Monsanto has known for decades the cancer-causing properties of Roundup and I applaud the jury for holding the company accountable for failing to warn consumers of the known danger."
"This verdict puts Bayer's back firmly up against the wall as the cost of litigation mounts and its stock price gets pummeled once again," he added.